Karsten Becker
Other
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Scientific MembershipsASM, DGHM, DGI, DMG, PEG, DGP, ESCMID
Publications
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5.87Impact points
The Length of the Staphylococcus aureus Protein A Polymorphic Region Regulates Inflammation: Impact on Acute and Chronic Infection.
The Journal of infectious diseases. 04/2012;
Staphylococcus aureus protein A (SpA) plays a critical role in the induction of inflammation. This study was aimed to determine whether the number of short sequence repeats (SSRs) present in the polymorphic region modulates the inflammatory response induced by SpA. We demonstrated that there is a do... [more] Staphylococcus aureus protein A (SpA) plays a critical role in the induction of inflammation. This study was aimed to determine whether the number of short sequence repeats (SSRs) present in the polymorphic region modulates the inflammatory response induced by SpA. We demonstrated that there is a dose-response effect in the activation of IFN-β signaling in airway epithelial and immune cells depending upon the number of SSRs which leads to differences in neutrophil recruitment. We also determined that a significant proportion of isolates from patients with chronic infections such as osteomyelitis and cystic fibrosis carry fewer SSRs than isolates from patients with acute infections or healthy carriers and there was an inverse correlation between the number of SSRs and the length of disease. Given the importance of IFN signaling in eradication of S. aureus, loss of SSRs may represent an advantageous mechanism to adapt to and persist in the host.
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4.16Impact points
Persistent blood stream infection with Kocuria rhizophila related to a damaged central catheter.
Journal of clinical microbiology. 01/2012;
A case of persistent blood stream infection with Kocuria rhizophila related to a damaged central venous catheter in a 3-year-old girl with Hirschprung's disease is reported. The strain was identified as K. rhizophila by 16S rRNA gene sequencing and matrix-assisted laser desorption/ionization-tim... [more] A case of persistent blood stream infection with Kocuria rhizophila related to a damaged central venous catheter in a 3-year-old girl with Hirschprung's disease is reported. The strain was identified as K. rhizophila by 16S rRNA gene sequencing and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Arbitrarily primed PCR analysis showed a clonal strain. The repeated septic episodes were resolved with the catheter repair.
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1.40Impact points
Species and susceptibility distribution of 1062 clinical yeast isolates to azoles, echinocandins, flucytosine and amphotericin B from a multi-centre study.
Mycoses. 01/2012;
Descriptive values were determined for eight antifungal agents within the course of a multi-centre study encompassing 1062 German and Austrian clinical yeast isolates. Candida albicans (54%) was the predominant species isolated followed by Candida glabrata (22%), Candida parapsilosis (6%), Candida t... [more] Descriptive values were determined for eight antifungal agents within the course of a multi-centre study encompassing 1062 German and Austrian clinical yeast isolates. Candida albicans (54%) was the predominant species isolated followed by Candida glabrata (22%), Candida parapsilosis (6%), Candida tropicalis (5.7%), Candida krusei (4.3%), as well as eleven further candidal and four non-Candida yeast species. While 519 (48.9%) isolates were tested susceptible to all antifungals tested, no isolate was found to exhibit complete cross resistance. For C. albicans, the proportions of susceptible isolates were 93.2% (amphotericin B), 95.6% (flucytosine), 84.3% (fluconazole), 83.8% (posaconazole), 91.8% (voriconazole), 96.5% (anidulafungin), 96.2% (caspofungin) and 97.6% (micafungin). Patterns of complete parallel resistances were observed within azoles (8.8%) and echinocandins (1.7%). While a decreased susceptibility was found infrequently for echinocandins and flucytosine, it was more common for azoles with highest proportions for isolates of C. glabrata (fluconazole, 40.6%; posaconazole, 37.2%), Candida guilliermondii (fluconazole and posaconazole, each 25.0%), C. krusei (posaconazole, 28.3%; voriconazole, 60%), C. parapsilosis (fluconazole, 70.3%) and C. tropicalis (fluconazole, 62.3%). The descriptive values obtained in this study represent a valid basis for the comparison of recent and future epidemiological surveys to analyse the susceptibility of yeast isolates towards major antifungal substances.
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4.41Impact points
Catheter Colonization and Abscess Formation Due to Staphylococcus epidermidis with Normal and Small-Colony-Variant Phenotype Is Mouse Strain Dependent.
PloS one. 01/2012; 7(5):e36602.
Coagulase-negative staphylococci (CoNS) form a thick, multilayered biofilm on foreign bodies and are a major cause of nosocomial implant-associated infections. Although foreign body infection models are well-established, limited in vivo data are available for CoNS with small-colony-variant (SCV) phe... [more] Coagulase-negative staphylococci (CoNS) form a thick, multilayered biofilm on foreign bodies and are a major cause of nosocomial implant-associated infections. Although foreign body infection models are well-established, limited in vivo data are available for CoNS with small-colony-variant (SCV) phenotype described as causative agents in implant-associated infections. Therefore, we investigated the impact of the Staphylococcus epidermidis phenotype on colonization of implanted PVC catheters and abscess formation in three different mouse strains. Following introduction of a catheter subcutaneously in each flank of 8- to 12-week-old inbred C57BL/6JCrl (B6J), outbred Crl:CD1(ICR) (CD-1), and inbred BALB/cAnNCrl (BALB/c) male mice, doses of S. epidermidis O-47 wild type, its hemB mutant with stable SCV phenotype, or its complemented mutant at concentrations of 10(6) to 10(9) colony forming units (CFUs) were gently spread onto each catheter. On day 7, mice were sacrificed and the size of the abscesses as well as bacterial colonization was determined. A total of 11,500 CFUs of the complemented mutant adhered to the catheter in BALB/c followed by 9,960 CFUs and 9,900 CFUs from S. epidermidis wild type in BALB/c and CD-1, respectively. SCV colonization was highest in CD-1 with 9,500 CFUs, whereas SCVs were not detected in B6J. The minimum dose that led to colonization or abscess formation in all mouse strains was 10(7) or 10(8) CFUs of the normal phenotype, respectively. A minimum dose of 10(8) or 10(9) CFU of the hemB mutant with stable SCV phenotype led to colonization only or abscess formation, respectively. The largest abscesses were detected in BALB/c inoculated with wild type bacteria or SCV (64 mm(2) vs. 28 mm(2)). Our results indicate that colonization and abscess formation by different phenotypes of S. epidermidis in a foreign body infection model is most effective in inbred BALB/c followed by outbred CD-1 and inbred B6J mice.
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2.80Impact points
Characterization of fusidic acid-resistant Staphylococcus aureus isolates in the community of Casablanca (Morocco).
International journal of medical microbiology : IJMM. 12/2011;
Resistance to fusidic acid in Staphylococcus aureus is caused by mutation of the elongation factor G (EF-G) encoded by fusA or by expression of a protein, encoded by fusB or fusC, that protects the drug target. Other mechanisms involved in this resistance are mutations in the riboprotein L6 operon w... [more] Resistance to fusidic acid in Staphylococcus aureus is caused by mutation of the elongation factor G (EF-G) encoded by fusA or by expression of a protein, encoded by fusB or fusC, that protects the drug target. Other mechanisms involved in this resistance are mutations in the riboprotein L6 operon within rplF. The aim of this study was to determine the prevalence and mechanisms of resistance to fusidic acid in clinical isolates of S. aureus in Casablanca (Morocco) and to define the phenotypic and genotypic traits of these isolates and their clonal relationship. All fusidic acid-resistant S. aureus (FAR-SA) isolates were tested for fusB and fusC genes and were evaluated for the detection of mutations in fusA and fusE (rplF). fusB-positive strains were tested for a cadDX operon, encoding cadmium resistance. The agr group and the presence of toxin genes were monitored to characterize all FAR-SA isolates which were typed by pulsed-field gel electrophoresis (PFGE) and spa typing. Among 140 clinical S. aureus isolates collected in 2007 and 2008, 18 (∼13%) exhibited resistance to fusidic acid. The most common resistance determinant was fusC, found in 16 isolates. Molecular typing showed that 14 of them harboured an agr group III and belonged to the same clonal complex (CC) spa type 127 and identical clonotype (cluster labelled A). These isolates also possessed the staphylococcal enterotoxin H gene. The second resistance determinant was fusB found in two isolates. These two isolates lacked cadDX gene and were found to belong to two unrelated clusters and spa types. While no isolate carrying mutations in rplF was found, 15 expressed a silent mutation in fusA (nucleotide 342). Only acquired fusidic acid resistance genes (mainly fusC) were prevalent among FAR-SA isolates with almost all of the clinical specimens belonging to CC-spa type 127. This study provides valuable data on the prevalence of fusidic acid-resistant S. aureus with the associated molecular mechanisms of resistance and the genetic background of the strains in Casablanca.
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3.01Impact points
Characteristics of hospital patients colonized with livestock-associated meticillin-resistant Staphylococcus aureus (MRSA) CC398 versus other MRSA clones.
The Journal of hospital infection. 12/2011; 79(4):292-6.
Meticillin-resistant Staphylococcus aureus (MRSA) associated with the clonal complex (CC) 398 has emerged among livestock and humans exposed to these animals. MRSA CC398 has so far contributed relatively little to spread of MRSA and the burden of disease in the healthcare setting. This study aimed t... [more] Meticillin-resistant Staphylococcus aureus (MRSA) associated with the clonal complex (CC) 398 has emerged among livestock and humans exposed to these animals. MRSA CC398 has so far contributed relatively little to spread of MRSA and the burden of disease in the healthcare setting. This study aimed to assess whether demographic and clinical differences in patients colonized with MRSA CC398 and those carrying other MRSA clones contribute to the observed differences in transmission and infection rates. Age, sex, length of stay (LOS), diagnoses and medical procedures were assessed in all patients with MRSA admitted to a university hospital in 2008 and 2009. S. aureus protein A gene (spa) typing was performed on the first MRSA isolate from each patient. Patients colonized or infected with MRSA that had spa types indicative of CC398 (MRSA CC398) were compared with patients who had other MRSA clones (MRSA non-CC398). Age (53 vs 59 years), mean LOS (8 vs 13 days) and percentage of patients admitted to an intensive care unit (12% vs 17%) differed significantly between MRSA CC398 and MRSA non-CC398 patients, respectively. The mean numbers and types of diagnoses and medical procedures performed for patients in these two groups also differed significantly. The differences in patient characteristics could explain, at least in part, the relatively low rates of transmission and infection associated with MRSA CC398 in the healthcare setting.
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The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in Germany.
Deutsches Ärzteblatt international. 11/2011; 108(45):761-7.
For decades, methicillin-resistant Staphylococcus aureus (MRSA) has been a major cause of infection in hospitals and nursing homes (health care-associated MRSA, HA-MRSA). Beginning in the late 1990s, many countries have also experienced a rising incidence of MRSA infection outside of the health care... [more] For decades, methicillin-resistant Staphylococcus aureus (MRSA) has been a major cause of infection in hospitals and nursing homes (health care-associated MRSA, HA-MRSA). Beginning in the late 1990s, many countries have also experienced a rising incidence of MRSA infection outside of the health care setting (community-associated MRSA, CA-MRSA). Moreover, animal reservoirs are increasingly considered to represent an important source of human MRSA acquisition. In this review article the authors describe the current epidemiological situation of MRSA in Germany. This review is based on pertinent articles published up to 2010 that were retrieved by a selective PubMed search, as well as on publications issued by national reference institutions up to 2010. There are about 132 000 cases of MRSA in German hospitals each year. MRSA is found in about 18% to 20% of all inpatient-derived culture specimens that are positive for S. aureus. CA-MRSA is not yet endemic in Germany; important risk factors for its acquisition include travel to high-prevalence areas and household contact with persons that harbor a CA-MRSA infection. Agricultural livestock is the main animal reservoir for MRSA, which is often zoonotically transmitted from animals to human beings by direct contact. However, both CA-MRSA and MRSA from animal reservoirs can be imported into hospitals and cause nosocomial infections. Hospitals and nursing homes were once the main reservoirs of MRSA, but new ones have now emerged outside of the healthcare setting. Efforts to prevent MRSA and limit its spread must rise to this new challenge.
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4.35Impact points
Comparative in vitro activity of finafloxacin against staphylococci displaying normal and small colony variant phenotypes.
The Journal of antimicrobial chemotherapy. 09/2011; 66(12):2809-13.
Staphylococcal small colony variants (SCVs) are associated with chronic and relapsing infections and their intracellular location may shield them from host defences and antibiotics. Finafloxacin is a novel fluoroquinolone that exhibits optimal activity at slightly acidic conditions where the activit... [more] Staphylococcal small colony variants (SCVs) are associated with chronic and relapsing infections and their intracellular location may shield them from host defences and antibiotics. Finafloxacin is a novel fluoroquinolone that exhibits optimal activity at slightly acidic conditions where the activity of other marketed fluoroquinolones decreases. Here, the in vitro activity of finafloxacin against clinical strain pairs consisting of an SCV and its clonally identical parental strain displaying the normal phenotype (NP) was compared with those of other fluoroquinolones at standard and low pH. In vitro activities of finafloxacin, ciprofloxacin, levofloxacin and moxifloxacin were tested against 28 methicillin-susceptible Staphylococcus aureus (MSSA) and three methicillin-resistant S. aureus (MRSA) SCV-NP strain pairs. Additionally, two S. aureus mutants (ΔhemB and ΔthyA) displaying the SCV phenotype and their wild-type strains as well as four SCV-NP pairs of coagulase-negative staphylococcal (CoNS) strains were included. MIC(50,) MIC(90) and MIC ranges were calculated based on MIC determination by Etest(®) at pH 5.8 and pH 7.2. Under acidic conditions, finafloxacin demonstrated superior activity against MSSA, MRSA and CoNS regardless of the phenotype. At neutral conditions, the activity against MSSA was as follows: moxifloxacin > finafloxacin > levofloxacin > ciprofloxacin. In comparison with methicillin-susceptible NP isolates, ciprofloxacin was less active against their corresponding SCVs. For other fluoroquinolones, there was no marked difference in activity against SCVs compared with NPs. Particularly in acidic body compartments, finafloxacin appears to be a promising new antibiotic for the treatment of persistent staphylococcal infections, including those caused by SCVs.
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3.60Impact points
Validating T-RFLP as a sensitive and high-throughput approach to assess bacterial diversity patterns in human anterior nares.
FEMS microbiology ecology. 09/2011; 79(1):98-108.
While recent works aimed to thoroughly characterize the bacterial community of the human anterior nares of a few candidates, this work sought to analyse a greater cross-section by sampling 100 volunteers. After optimizing and validating the method of terminal restriction fragment length polymorphism... [more] While recent works aimed to thoroughly characterize the bacterial community of the human anterior nares of a few candidates, this work sought to analyse a greater cross-section by sampling 100 volunteers. After optimizing and validating the method of terminal restriction fragment length polymorphism against six previously pyrosequenced samples, abundant species could be discriminated and their relative abundances measured in a high-throughput manner. The 100 volunteers could be statistically clustered into 12 groups, where two-thirds of volunteers shared more than 40% similarity in respect to their bacterial community structure, while the remaining third clustered into smaller groups being dominated by Dolosigranulum pigrum, Moraxella spp. or Staphylococcus aureus. Moraxella spp. was present predominantly in women rather than in men. The use of network analysis charting bacterial ecological co-occurrences revealed new evidence of likely positive associations between some core human nasal species. So, in the age of post 'omics' and 'deep sequencing', there is still a place for these well-tried and well-tested methods that can offer a rapid, reproducible and economical alternative, whereby also yielding valuable new information.
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4.80Impact points
In vitro activity against Staphylococcus aureus of a novel antimicrobial agent, PRF-119, a recombinant chimeric bacteriophage endolysin.
Antimicrobial agents and chemotherapy. 09/2011; 55(9):4416-9.
Antistaphylococcal activity of the novel chimeric endolysin PRF-119 was evaluated with the microdilution method. The MIC(50) and MIC(90) of 398 methicillin-susceptible Staphylococcus aureus isolates were 0.098 μg/ml and 0.391 μg/ml, respectively (range, 0.024 to 0.780 μg/ml). Both the MIC(50) and MI... [more] Antistaphylococcal activity of the novel chimeric endolysin PRF-119 was evaluated with the microdilution method. The MIC(50) and MIC(90) of 398 methicillin-susceptible Staphylococcus aureus isolates were 0.098 μg/ml and 0.391 μg/ml, respectively (range, 0.024 to 0.780 μg/ml). Both the MIC(50) and MIC(90) values of 776 methicillin-resistant S. aureus isolates were 0.391 μg/ml (range, 0.024 to 1.563 μg/ml). All 192 clinical isolates of coagulase-negative staphylococci exhibited MIC values of >50 μg/ml. In conclusion, PRF-119 exhibited very good activity specifically against S. aureus.
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2.76Impact points
Auxotrophic mutant of Staphylococcus aureus interferes with nasal colonization by the wild type.
Microbes and infection / Institut Pasteur. 07/2011; 13(12-13):1081-90.
Staphylococcus aureus nasal carriage is a risk factor for infection in humans, particularly in the hospital setting. Bacterial interference was used as an alternative strategy for the prevention of upper respiratory, urogenital and gastrointestinal tract infections. This study was designed to assess... [more] Staphylococcus aureus nasal carriage is a risk factor for infection in humans, particularly in the hospital setting. Bacterial interference was used as an alternative strategy for the prevention of upper respiratory, urogenital and gastrointestinal tract infections. This study was designed to assess if the administration of a live-attenuated aroA mutant of S. aureus is useful as a potential approach to prevent transient staphylococcal nasal carriage by virulent strains. We constructed an aroA mutant of S. aureus Newman strain by homologous recombination. The auxotrophic NK41 mutant was attenuated as determined by the increase of the LD(50) after intraperitoneal challenge. In mice, previous nasal colonization with the NK41 mutant significantly reduced the number of CFU of S. aureus (HU-71 and Hde288) clinical isolates and the parental Newman strain. The NK41 mutant was unable to induce a pro-inflammatory response and to damage the invaded human respiratory epithelial cells. Moreover, the cells previously or simultaneously infected with the NK41 mutant were invaded by virulent strains in a significantly lower degree than those of the control group. In conclusion, the attenuated NK41 mutant interfered with the colonization and establishment of pathogenic strains of S. aureus, which produce severe infections.
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4.43Impact points
Small colony variants of Staphylococcus aureus reveal distinct protein profiles.
Proteomics. 06/2011; 11(12):2476-90.
Small-colony variants (SCVs) of Staphylococcus aureus represent a slow-growing subpopulation causing chronic and relapsing infections due to their physiological adaptation on an intracellular lifestyle. In this first proteomic study on physiological changes associated with a natural, clinically deri... [more] Small-colony variants (SCVs) of Staphylococcus aureus represent a slow-growing subpopulation causing chronic and relapsing infections due to their physiological adaptation on an intracellular lifestyle. In this first proteomic study on physiological changes associated with a natural, clinically derived SCV, its proteomic profile was investigated in comparison to corresponding isogenic strains displaying normal (clinical wild-type strain, complemented hemB mutant and spontaneous revertant of the clinical SCV) and SCV phenotypes (hemB mutant and gentamicin-induced SCV). Applying an ultra-high resolution chromatography and high mass accuracy MS(E) -based label-free relative and absolute protein quantification approach, the whole cytoplasmic proteome of this strain sextet was investigated in a growth phase-controlled manner covering early-exponential, late-exponential and stationary phases. Of 1019 cytoplasmic proteins identified, 154 were found to be differently regulated between strains. All SCV phenotypes showed down-regulation of the tricarboxylic acid (TCA) cycle-related proteins and of a protein cluster involved in purine/pyrimidine and folate metabolism. In contrast to hemB mutant and gentamicin-induced SCVs, the clinically derived SCVs showed no prominent up-regulation of glycolytic proteins. The spontaneous switch into the normal phenotype resulted in up-regulation of TCA cycle-related parts, while oxidative stress-related proteins were down-regulated. However, the natural revertant from the clinical SCV retained also dominant protein features of the clinical SCV phenotype. In conclusion, physiological changes between normal and SCV S. aureus phenotypes are more complex than reflected by defined electron transport chain-interrupting mutants and their complemented counterparts.
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1.25Impact points
IKK-2 inhibitor TPCA-1 represses nasal epithelial inflammation in vitro.
Rhinology. 06/2011; 49(2):168-73.
Nasal polyposis (NP) is considered a subgroup within chronic rhinosinusitis. NP can be further subdivided into aspirin sensitive- and aspirin tolerant types (ASNP/ ATNP). Although the true etiology of NP has not been identified so far, it is agreed that NP represents an inflammatory disease of the n... [more] Nasal polyposis (NP) is considered a subgroup within chronic rhinosinusitis. NP can be further subdivided into aspirin sensitive- and aspirin tolerant types (ASNP/ ATNP). Although the true etiology of NP has not been identified so far, it is agreed that NP represents an inflammatory disease of the nasal mucosa. Alterations of cellular kinase activities including that of IKK-2 might play a role in this inflammatory process. Paraffin sections of ASNP, ATNP and controls were immunostained with Phospho-IkB-α antibody that detects the direct IKK-2 product (IkB-α. Intensity of epithelial staining was analysed semi-quantitatively by two independent observers. In cultured nasal polyp epithelial cells (NPECs) epithelial derived cytokines IL-8 and GRO α were induced by TNF-α or Staphylococcal supernatants and subsequently repressed by IKK-2 inhibitor TPCA-1. Significant Phospho-IkB-α staining was observed in the nasal epithelium of ASNP compared to ATNP and controls suggesting strong IKK-2 activation in patients with ASNP in vivo. In vitro, pro-inflammatory cytokines IL-8 and GRO-α in NPECs were significantly repressed by TPCA-1. IKK-2 activity is increased in the subgroup of ASNP. IL-8 and GRO-α responses were repressed by IKK-2 inhibitor TPCA-1 in vitro. IKK-2 inhibitors might represent a potential target for anti-inflammatory intervention in ASNP.
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4.01Impact points
Virulence factors and genotypes of Staphylococcus aureus from infection and carriage in Gabon.
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 04/2011; 17(10):1507-13.
Staphylococcus aureus isolates from developed countries have been extensively analyzed with respect to their virulence patterns and clonal relatedness but there is only sparse information on the molecular diversity of S. aureus isolates from Africa. In particular, little is known about S. aureus iso... [more] Staphylococcus aureus isolates from developed countries have been extensively analyzed with respect to their virulence patterns and clonal relatedness but there is only sparse information on the molecular diversity of S. aureus isolates from Africa. In particular, little is known about S. aureus isolates from asymptomatic carriers compared with isolates causing infections. From 2008 to 2010, we prospectively collected S. aureus isolates from asymptomatic carriers and infections in Lambaréné, Gabon, Central Africa. For these isolates, we determined major virulence factors, and performed multilocus sequence typing (MLST) and spa typing. Among 163 S. aureus isolates from asymptomatic carriers, we found the MLST clonal complexes (CCs) 5, 6, 7, 8, 9, 15, 25, 30, 45, 88, 101, 121 and 152; 3.7% were methicillin-resistant (MRSA). The clinical isolates were associated with CCs 5, 8, 9, 15, 88, 121 and 152; 11% were MRSA. Sequence types 1 and 88 were significantly associated with infection and sequence type 508 was associated with carriage. Remarkably, there was a high prevalence of Panton-Valentine leukocidin (PVL) -encoding genes both in disease-related isolates (57.4%) and in carrier isolates (40.5%). We found differences in the clonal structure and virulence pattern of Gabonese S. aureus isolates from asymptomatic carriers and infections. Of note, S. aureus isolates from Gabon show a very high prevalence of PVL-encoding genes, which exceeds the rates observed for developed countries.
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2.61Impact points
Resistance trends and in vitro activity of tigecycline and 17 other antimicrobial agents against Gram-positive and Gram-negative organisms, including multidrug-resistant pathogens, in Germany.
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 02/2011; 30(9):1095-103.
To document the development of resistance to tigecycline in comparison with 17 other antimicrobials, the susceptibilities of 2,741 isolates comprising 16 bacterial species recovered from hospitalised patients in 15 German centres in 2009 were assessed. The results were compared with those of previou... [more] To document the development of resistance to tigecycline in comparison with 17 other antimicrobials, the susceptibilities of 2,741 isolates comprising 16 bacterial species recovered from hospitalised patients in 15 German centres in 2009 were assessed. The results were compared with those of previous trials (German Tigecycline Evaluation Surveillance Trial, G-TEST I and II, performed in 2005 and 2007, respectively) conducted prior to and shortly after the introduction of tigecycline in Germany. Moreover, the in vitro activities of tigecycline against the subset of multidrug-resistant (MDR) pathogens recovered within all three sampling periods (n = 4,988) were evaluated in comparison to the corresponding non-MDR isolates. All susceptibility tests were performed by broth microdilution. Between 2005 and 2009, tigecycline retained its high activity against Gram-positive and Gram-negative organisms, including MDR pathogens. By contrast, an in part marked increase in resistance to broad-spectrum beta-lactams and fluoroquinolones was observed for many Enterobacteriaceae and for non-fermenting Gram-negative bacteria. Against a background of a steadily increasing number of multiresistant pathogens, the activity of tigecycline remained unaltered. With the exception of Acinetobacter isolates with decreased susceptibility to carbapenems, tigecycline's activity profile was not notably affected by organisms resistant to other drug classes and, thus, holds promise as an important therapeutic agent, particularly for situations in which MDR organisms are suspected.
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Staphylococcus aureus phenotype switching: an effective bacterial strategy to escape host immune response and establish a chronic infection.
EMBO molecular medicine. 01/2011; 3(3):129-41.
Staphylococcus aureus is a frequent cause for serious, chronic and therapy-refractive infections in spite of susceptibility to antibiotics in vitro. In chronic infections, altered bacterial phenotypes, such as small colony variants (SCVs), have been found. Yet, it is largely unclear whether the abil... [more] Staphylococcus aureus is a frequent cause for serious, chronic and therapy-refractive infections in spite of susceptibility to antibiotics in vitro. In chronic infections, altered bacterial phenotypes, such as small colony variants (SCVs), have been found. Yet, it is largely unclear whether the ability to interconvert from the wild-type to the SCV phenotype is only a rare clinical and/or just laboratory phenomenon or is essential to sustain an infection. Here, we performed different long-term in vitro and in vivo infection models with S. aureus and we show that viable bacteria can persist within host cells and/or tissues for several weeks. Persistence induced bacterial phenotypic diversity, including SCV phenotypes, accompanied by changes in virulence factor expression and auxotrophism. However, the recovered SCV phenotypes were highly dynamic and rapidly reverted to the fully virulent wild-type form when leaving the intracellular location and infecting new cells. Our findings demonstrate that bacterial phenotype switching is an integral part of the infection process that enables the bacteria to hide inside host cells, which can be a reservoir for chronic and therapy-refractive infections.
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2.80Impact points
The matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS)-based protein peaks of 4448 and 5302 Da are not associated with the presence of Panton-Valentine leukocidin.
International journal of medical microbiology : IJMM. 01/2011; 301(1):58-63.
The Panton-Valentine leukocidin (PVL) of Staphylococcus aureus plays an important role in the pathogenesis of necrotizing pneumonia and recurrent skin and soft tissue infections. The gene encoding for PVL, lukS/F-PV, is distributed by prophages and can thus spread between isolates. Molecular methods... [more] The Panton-Valentine leukocidin (PVL) of Staphylococcus aureus plays an important role in the pathogenesis of necrotizing pneumonia and recurrent skin and soft tissue infections. The gene encoding for PVL, lukS/F-PV, is distributed by prophages and can thus spread between isolates. Molecular methods have normally been used to identify lukS/F-PV-positive strains. Recently, however, a matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS)-based method has been described to identify PVL-positive S. aureus strains. The aim of this study was thus to investigate the association of distinct MALDI-TOF MS peaks to the toxin profile in molecularly characterized methicillin-susceptible (MSSA) and methicillin-resistant S. aureus (MRSA) strains harbouring lukS/F-PV. In contrast to the previous results, the MALDI-TOF MS peaks were detected in all 104 recently described molecularly divergent MRSA irrespective of the presence of PVL. Our result indicates that these described peaks seem to be independent of the presence of PVL.
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4.69Impact points
Population structure of Staphylococcus aureus from remote African Babongo Pygmies.
PLoS neglected tropical diseases. 01/2011; 5(5):e1150.
Pandemic community-acquired methicillin-resistant Staphylococcus aureus isolates (CA-MRSA) predominantly encode the Panton-Valentine leukocidin (PVL), which can be associated with severe infections. Reports from non-indigenous Sub-Saharan African populations revealed a high prevalence of PVL-positiv... [more] Pandemic community-acquired methicillin-resistant Staphylococcus aureus isolates (CA-MRSA) predominantly encode the Panton-Valentine leukocidin (PVL), which can be associated with severe infections. Reports from non-indigenous Sub-Saharan African populations revealed a high prevalence of PVL-positive isolates. The objective of our study was to investigate the S. aureus carriage among a remote indigenous African population and to determine the molecular characteristics of the isolates, particularly those that were PVL-positive. Nasal S. aureus carriage and risk factors of colonization were systematically assessed in remote Gabonese Babongo Pygmies. Susceptibility to antibiotics, possession of toxin-encoding genes (i.e., PVL, enterotoxins, and exfoliative toxins), S. aureus protein A (spa) types and multi-locus sequence types (MLST) were determined for each isolate. The carriage rate was 33%. No MRSA was detected, 61.8% of the isolates were susceptible to penicillin. Genes encoding PVL (55.9%), enterotoxin B (20.6%), exfoliative toxin D (11.7%) and the epidermal cell differentiation inhibitor B (11.7%) were highly prevalent. Thirteen spa types were detected and were associated with 10 STs predominated by ST15, ST30, ST72, ST80, and ST88. The high prevalence of PVL-positive isolates among Babongo Pygmies demands our attention as PVL can be associated with necrotinzing infection and may increase the risk of severe infections in remote Pygmy populations. Many S. aureus isolates from Babongo Pygmies and pandemic CA-MRSA-clones have a common genetic background. Surveillance is needed to control the development of resistance to antibiotic drugs and to assess the impact of the high prevalence of PVL in indigenous populations.
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5.87Impact points
Staphylococcus aureus small-colony variants are adapted phenotypes for intracellular persistence.
The Journal of infectious diseases. 10/2010; 202(7):1031-40.
Staphylococcus aureus is an important human pathogen of endovascular diseases, which can take a chronic course with a high relapse rate despite antimicrobial treatment. Thus far, persistent and antibiotic-refractory infections have been largely associated with a subpopulation of S. aureus, the small... [more] Staphylococcus aureus is an important human pathogen of endovascular diseases, which can take a chronic course with a high relapse rate despite antimicrobial treatment. Thus far, persistent and antibiotic-refractory infections have been largely associated with a subpopulation of S. aureus, the small-colony variants (SCVs). In this work, we used endothelial cells to investigate infection with the highly virulent wild-type isolate (6850), 2 stable isogenic SCV phenotypes (hemB mutant IIb13 and JB1), and the complemented mutant. All strains were highly invasive in endothelial cells but largely differed in host response induction. Microarray analysis showed that wild-type phenotypes up-regulated a large number of endothelial genes (including genes involved in innate immunity), whereas the SCVs did not cause these dramatic changes. The inflammatory response and cytotoxicity were strongest shortly after infection and largely decreased within the following days, which was accompanied by a fast elimination of intracellular wild-type bacteria. By contrast, SCVs survived within endothelial cells at high numbers. S. aureus intracellular persistence via the development of an adapted subpopulation of SCVs most likely represents an important strategy of S. aureus to hide within the host cells, which could be a reservoir for chronic infections.
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5.54Impact points
Subcutaneous infection with S. aureus in mice reveals association of resistance with influx of neutrophils and Th2 response.
The Journal of investigative dermatology. 09/2010; 131(1):125-32.
Staphylococcus aureus is the leading cause of bacterial skin infection. Once it overcomes the epithelial barrier, it either remains locally controlled or spreads in the dermis causing soft tissue infection. These different courses depend not only on its virulence factors, but also on the immune resp... [more] Staphylococcus aureus is the leading cause of bacterial skin infection. Once it overcomes the epithelial barrier, it either remains locally controlled or spreads in the dermis causing soft tissue infection. These different courses depend not only on its virulence factors, but also on the immune response of the infected individual. The goal of this study was to identify host factors that influence different outcomes. We, therefore, established comparative analysis of subcutaneous footpad infection with S. aureus (SH1000) in different inbred mouse strains. We found that C57BL/6 mice are more susceptible than BALB/c and DBA/2 mice, reflected by significantly higher footpad swelling and bacterial load, as well as increased dissemination of bacteria into inguinal lymph nodes and kidneys. This susceptibility was associated with lower influx of polymorphonuclear leukocytes (PMNs), but higher secretion of CXCL-2. Remarkably, resistance correlated with S. aureus-specific Th2-cell response in BALB/c and DBA/2 mice, whereas susceptible C57BL/6 mice generated a Th1-cell response. As Th1 cells are able to induce release of CXCL-2, and as CXCL-2 is able to increase the survival of S. aureus within PMNs, interactions between PMNs and Th1 or Th2 cells need to be considered as important mechanisms of resistance in murine soft tissue infection with S. aureus.
Following (4)
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Bhanu Sinha
Julius-Maximilians-Universität Würzburg -
Nicole von Maltzahn
Institute for Med. Microbiology, Hannover Medical School -
Didier Moissenet
Université Pierre et Marie Curie Paris 6 -
Florian Szabados
Ruhr-Universität Bochum
