International journal of medical microbiology: IJMM

Publications in this journal

• Article: The P-type ATPase Spf1 is required for endoplasmic reticulum functions and cell wall integrity in Candida albicans.

  Qilin Yu, Xiaohui Ding, Bing Zhang, Ning Xu, Xinxin Cheng, Kefan Qian, Biao Zhang, Laijun Xing, Mingchun Li
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  ABSTRACT: Endoplasmic reticulum (ER) is crucial for protein folding, glycosylation and secretion in eukaryotic organisms. These important functions are supported by high levels of Ca(2+) in the ER. We have recently identified a putative ER Ca(2+) pump in Candida albicans, called Spf1, which plays key roles in maintenance of cellular Ca(2+) homeostasis, morphogenesis and virulence. In this study, we purified Spf1 and confirmed that it is a P-type ATPase, suggesting its role in maintaining high levels of ER Ca(2+). Disruption of SPF1 caused severe defects in glycosylation of the ER-localized protein Cdc101 and secretory acid phosphatase, and a decrease in expression of SEC61 which encodes an important ER protein. Moreover, the spf1Δ/Δ mutant showed increased sensitivity to cell wall stresses, abnormal cell wall composition, delayed cell wall reconstruction and decreased flocculation and adherence, indicating its defect in cell wall integrity (CWI). We also revealed that disruption of SPF1 has an impact on gene expression related to CWI and morphogenesis. This study provides evidence that Spf1, as a P-type ATPase, is essential for ER functions and consequent CWI, implicating a role of ER Ca(2+) homeostasis in C. albicans physiology.
  International journal of medical microbiology: IJMM 05/2013;
• Article: Immunogenicity of Pasteurella multocida and Mannheimia haemolytica outer membrane vesicles.

  Sandro Roier, Judith C Fenninger, Deborah R Leitner, Gerald N Rechberger, Joachim Reidl, Stefan Schild
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  ABSTRACT: Pasteurella multocida is able to cause disease in humans and in a wide range of animal hosts, including fowl cholera in birds, atrophic rhinitis in pigs, and snuffles in rabbits. Together with Mannheimia haemolytica, P. multocida also represents a major bacterial causative agent of bovine respiratory disease (BRD), which is one of the most important causes for economic losses for the cattle backgrounding and feedlot industry. Commercially available vaccines only partially prevent infections caused by P. multocida and M. haemolytica. Thus, this study characterized the immunogenicity of P. multocida and M. haemolytica outer membrane vesicles (OMVs) upon intranasal immunization of BALB/c mice. Enzyme-linked immunosorbent assays (ELISA) revealed that OMVs derived from P. multocida or M. haemolytica are able to induce robust humoral and mucosal immune responses against the respective donor strain. In addition, also significant cross-immunogenic potential was observed for both OMV types. Colonization studies showed that a potential protective immune response against P. multocida is not only achieved by immunization with P. multocida OMVs, but also by immunization with OMVs derived from M. haemolytica. Immunoblot and immunoprecipitation analyses demonstrated that M. haemolytica OMVs induce a more complex immune response compared to P. multocida OMVs. The outer membrane proteins OmpA, OmpH, and P6 were identified as the three major immunogenic proteins of P. multocida OMVs. Amongst others, the serotype 1-specific antigen, an uncharacterized outer membrane protein, as well as the outer membrane proteins P2 and OmpA were found to be the most important antigens of M. haemolytica OMVs. These findings are useful for the future development of broad-spectrum OMV based vaccines against BRD and other infections caused by P. multocida or M. haemolytica.
  International journal of medical microbiology: IJMM 05/2013;
• Article: Bacteria of the genus Dyella can chronically colonise the airways of patients with cystic fibrosis and elicit a pronounced antibody response.

  Liv M Duus, Niels Høiby, Mikala Wang, Oluf Schiøtz, Niels Nørskov-Lauritsen
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  ABSTRACT: A patient with cystic fibrosis became chronically colonised with an unusual non-fermenting Gram-negative rod that could be cultured on Burkholderia cepacia selective agar. Phenotypic characterisation by VITEK-2 suggested identification as Elizabethkingia meningoseptica, however 16S rRNA gene sequencing revealed it belonged to a putative novel species of genus Dyella. Thirty months after the initial detection, the patient produced a high level of precipitating antibodies against the bacterium.
  International journal of medical microbiology: IJMM 05/2013;
• Article: Antibiotic consumption and resistance: Data from Europe and Germany.

  Elisabeth Meyer, Petra Gastmeier, Maria Deja, Frank Schwab
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  ABSTRACT: The use of antibiotics - including the over- and misuse - in human and veterinary practices selected for resistant pathogens and led to their emergence and dissemination along with the transmission of resistant bacteria. The aim of this article is to prescribe the prerequisites for the surveillance of antibiotic use and bacterial resistance, to explain advantage and disadvantage of surveillance parameters used, to present new data from a surveillance network of intensive care units focusing on antibiotic use and resistance and to discuss the impact of antibiotic use on resistance. The Surveillance System of Antibiotic Use and Bacterial Resistance in Intensive Care Units (SARI) is an on-going project that collects data from its network of intensive care units (ICU) in Germany. Antimicrobial use was expressed as daily defined doses (DDD) and normalized per 1000 patient-days (pd). ICU decided either to provide monthly data on antibiotic and resistant pathogens or they decided to provide only yearly data on antibiotic use without resistance data. 85% of all antibiotics used in Germany are administered in animals; 85% of the antibiotics used in humans are prescribed in the outpatient setting and 85% of the antibiotics used in hospitals are prescribed on non-ICUs wards. The mostly widely used parameter for the surveillance of resistance is the percentage of resistant pathogens which is important to guide empirical therapy but does not measure the burden of resistance which is of interest to the public health perspective. The burden of MRSA did not increase over the last 11 years in ICUs and was 4.2MRSA/1000pd in 2011. The burden of 3rd generation resistant E. coli and K. pneumoniae more than quintupled (up to 2.6 and 1.2 respectively) and was followed by a three times increased use of carbapenems and correlated with quinolone and 3rd generation cephalosporin use. The burden VRE faecium also increased dramatically from 0.1 to 0.8 within 11 years; VRE faecium showed no significant correlation to vancomycin use (p=0.190) although glycopeptide use increased lately. Antibiotic use in animals and humans correlates with the risk of resistant microorganisms in a multifactor and complex way; it is of upmost importance that surveillance and interventions focus on all sectors: animal use and in- and outpatient setting in humans.
  International journal of medical microbiology: IJMM 04/2013;
• Article: Livestock associated MRSA (LA-MRSA) and its relevance for humans in Germany.

  Christiane Cuny, Robin Köck, Wolfgang Witte
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  ABSTRACT: Livestock-associated Staphylococcus aureus (LA-MRSA) are mainly associated with the clonal complex (CC) 398. Although having its main reservoir as MRSA in livestock such as pigs, poultry or cattle LA-MRSA CC398 has no pronounced host specificity and can colonize or infect other animals such as horses and dogs and also humans. In German conventional farming systems nasal colonization of the animals and of humans occupationally exposed to them (up to 86%) are frequent. Further human-to-human dissemination in households occurs more rarely in general (∼4% of humans living on farms but without occupational exposition). Nasal colonization with LA-MRSA of humans at hospital admission is found in 0.08-0.2% for Germany in general. However, this proportion is higher in areas with a high density of livestock production such as in northwestern North Rhine-Westphalia or Lower Saxony. LA-MRSA CC398 is not less pathogenic for humans than S. aureus in general. Hence, LA-MRSA accounts for ∼15% of all MRSA isolates from deep-seated skin and soft-tissue infections in the community and for about 0.8-2% of all MRSA isolated from clinical specimens obtained in hospital settings. When introduced into the hospital it can cause postoperative wound infections and even septicemia. Differently from hospital-associated MRSA clones, LA-MRSA CC398 has obviously limited capacity to spread in the nosocomial setting so far (proportion of ∼1.8% among MRSA from nosocomial infections, the proportion among MRSA from blood cultures is ∼1%).
  International journal of medical microbiology: IJMM 04/2013;
• Article: Fluorescence in situ hybridization (FISH) for rapid identification of Salmonella spp. from agar and blood culture broth-An option for the tropics?

  Hagen Frickmann, Andrea Hänle, Andreas Essig, Denise Dekker, Kennedy Boahen, Samuel Acquah, Nimako Sarpong, Yaw Adu-Sarkodie, Norbert G Schwarz, Jürgen May, Florian Marks, Ralf M Hagen, Sven Poppert
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  ABSTRACT: BACKGROUND: Salmonella enterica is an important cause of diarrhea with the potential to cause systemic infection including sepsis, particularly in the tropics. Sepsis in particular requires quick and reliable identification to allow a rapid optimization of antibiotic therapy. We describe the establishment and evaluation of fluorescence in situ hybridization (FISH) as a rapid and easy-to-perform molecular identification procedure from agar and blood culture broths. METHODS: Two newly developed FISH probes with specificity for Salmonella spp. were evaluated with 10 reference strains, 448 clinical isolates of Gram-negative bacteria from Germany and Ghana including 316 Salmonella spp. strains, and 39 environmental Salmonella spp. isolates from rivers and streams in Ghana. One FISH probe was further tested with 207 pre-incubated blood culture broths from Germany with Gram-negative rod-shaped bacteria in Gram stain. RESULTS: Evaluation of the newly designed FISH probes demonstrated sensitivity of 99.2% and specificity of 98.4% for clinical isolates, sensitivity of 97.4% for environmental Salmonella spp. isolates, and sensitivity of 100% and specificity of 99.5% for blood culture materials. CONCLUSIONS: FISH proved to be highly reliable for a rapid identification of Salmonella spp. directly from pre-incubated blood culture broths as well as after growth on agar. The inexpensive and easy-to-perform procedure is particularly suitable for resource-limited areas where more sophisticated procedures are not available.
  International journal of medical microbiology: IJMM 04/2013;
• Article: Host metabolism promotes growth of Chlamydia pneumoniae in a low oxygen environment.

  Márta Szaszák, Kensuke Shima, Nadja Käding, Michael Hannus, Werner Solbach, Jan Rupp
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  ABSTRACT: Chlamydia pneumoniae infections of the respiratory tract are common and are associated with acute and chronic diseases such as community-acquired pneumonia (CAP) and chronic obstructive pulmonary disease (COPD). Recent studies have shown that reduced environmental oxygen availability promotes chlamydial growth in infected host cells. The underlying mechanisms remain unclear. We performed a targeted siRNA screen coupled with an automated high-throughput microscopic analysis to identify key host cell genes that play a role in promoting the hypoxic growth of C. pneumoniae. A total of 294 siRNAs - targeting 98 selected genes including central mediators of metabolic, trafficking and signaling pathways - were tested on chlamydial inclusion formation in C. pneumoniae infected A549 cells under normoxic (20% O2) and hypoxic (2% O2) conditions 48h post infection. Evaluation of the different functional clusters of genes revealed that under hypoxic conditions, enhanced growth of C. pneumoniae was centrally mediated by the host cell glycolytic pathway. Inhibition of the phosphofructokinase (PFK), lactate dehydrogenase (LDH), glycerol-3-phosphate dehydrogenase (GPD2) and the forkheadbox O3 (FOXO3) gene-expression by siRNAs abrogated chlamydial progeny. The pivotal role of host cell glycolysis in chlamydial development under hypoxia was further confirmed by pharmacological inhibition of the pathway by 2-fluoro-deoxy-glucose. The results indicate that the microenvironment of the host cell determines the fate of C. pneumoniae by controlling pathogen-induced metabolic pathways.
  International journal of medical microbiology: IJMM 04/2013;
• Article: Methylthioadenosine/S-adenosylhomocysteine nucleosidase (Pfs) of Staphylococcus aureus is essential for the virulence independent of LuxS/AI-2 system.

  Yan Bao, Yajuan Li, Qiu Jiang, Liping Zhao, Ting Xue, Bing Hu, Baolin Sun
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  ABSTRACT: Staphylococcus aureus is a major cause of infectious morbidity and mortality in both community and hospital settings. The bacterium continues to cause diverse invasive, life-threatening infections, such as pneumonia, endocarditis, and septicemia. Methylthioadenosine/S-adenosylhomocysteine nucleosidase (Pfs) is predicted to be an important enzyme involved in methylation reactions, polyamine synthesis, vitamin synthesis, and quorum sensing pathways. For the first time, we demonstrate that Pfs is essential for the virulence of S. aureus. The pfs mutant strain, as compared to the isogenic wild type, displayed a decreased production of extracellular proteases, which was correlated with a dramatic decrease in the expression of the sspABC operon and a moderate decrease of aur expression. The mouse model of sepsis and subcutaneous abscesses indicated that the pfs mutant strain displayed highly impaired virulence compared to the isogenic wild type. The decreased virulence of the pfs mutant strain is in correspondence with its decreased proliferation in vivo, indicated with a real-time analysis in the transparent system of zebrafish embryos. These phenotypes of the pfs mutant strain are LuxS/AI-2 independent despite the essential role pfs plays in AI-2 production. Our data suggest that Pfs is a potential novel target for anti-infection therapy.
  International journal of medical microbiology: IJMM 03/2013;
• Article: Molecular epidemiology of plasmid-mediated high-level mupirocin resistance in methicillin-resistant Staphylococcus aureus in four Spanish health care settings.

  Eduardo Pérez-Roth, Carmen Potel-Alvarellos, Xiomara Espartero, Lucia Constela-Caramés, Sebastián Méndez-Álvarez, Maximiliano Alvarez-Fernández
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  ABSTRACT: Mupirocin is used for the decolonization of methicillin-resistant Staphylococcus aureus (MRSA). High-level mupirocin resistance (Hi-Mup(R)) is of concern, having been associated with therapeutic failure. Our main objective was to assess the emergence and mode/s of spread of Hi-Mup(R) in the MRSA population recovered between 2002 and 2009 in four health care settings in the Pontevedra province, northwest Spain. Five hundred and fifty consecutive clinical MRSA isolates were obtained and screened for antimicrobial susceptibility. Isolates were stratified into multidrug-resistant (MDR) and non-MDR. High-level mupirocin resistant MRSA were characterized by genotyping and plasmid analysis. Thirty-one MRSA (5.6%) exhibited Hi-Mup(R). No association was detected between Hi-Mup(R) and MDR but isolates displaying Hi-Mup(R) were more likely to be resistant to gentamicin and tobramycin. Four main MRSA clones were identified: ST125/t067/PFGE A, ST36/t018/PFGE D, ST8/t008/PFGE B, and ST72/t148 or t3092/PFGE B. Each isolate carried the Hi-Mup(R)ileS2-encoding gene on plasmids and ten plasmid types were distinguished based on unique IS257-ileS2 configurations. Some plasmid types were successfully disseminated among the MRSA clones. Remarkably, six plasmid types were acquired by the predominant genotype ST125/t067/PFGE A. In conclusion, molecular characterization of MRSA isolates combined with the rapid typing of ileS2-encoding plasmids through determination of IS257-ileS2 configurations have proved to be a powerful strategy to address the molecular epidemiology of Hi-Mup(R). The transmission of a diverse set of ileS2-carrying plasmids promoted the emergence of the resistance, with a limited role of clonal expansion in its dispersion.
  International journal of medical microbiology: IJMM 03/2013;
• Article: Rapid identification of bacterial and fungal pathogens from positive blood cultures by MALDI-TOF MS.

  Christian Leli, Elio Cenci, Angela Cardaccia, Amedeo Moretti, Francesco D'Alò, Rita Pagliochini, Mariella Barcaccia, Senia Farinelli, Simona Vento, Francesco Bistoni, Antonella Mencacci
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  ABSTRACT: Sepsis is a syndrome characterized by a systemic inflammatory response due to severe infection. Early detection of causal agents and appropriate antimicrobial treatment reduce mortality. Conventional microbiological methods often do not provide time critical results for an optimal early management. We used an in-house protocol based on Tween 80 to process 109 positive blood cultures for bacteria and yeast identification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), and results were compared to standard reference or automated methods. MALDI-TOF MS correctly identified 91.7% of the isolates. Correct identification was obtained for 57/62 (91.9%) aerobic/facultative anaerobic Gram-positive isolates, 53 (85.5%) at species level, and 4 (6.4%) at the genus level; 32/32 (100%) aerobic/facultative anaerobic Gram-negative isolates, 31 (96.9%) at species level, and 1 (3.1%) at the genus level; 7/7 (100%) obligate anaerobes, all at the genus level; 3/7 (42.8%) fungi, all at genus level. Overall, the median identification time of MALDI-TOF MS vs reference standard methods was significantly shorter: median (interquartile range) 7.1h (4.7-10.2) vs 48.1h (32.5-50.0), p<0.0001. MALDI-TOF MS is a valuable tool for rapid identification of pathogens in septic patients. An in-house protocol based on Tween 80 can be used to process positive blood cultures.
  International journal of medical microbiology: IJMM 03/2013;
• Article: Molecular epidemiology and resistance profiles of Clostridium difficile in a tertiary care hospital in Spain.

  Irene Weber, Elena Riera, Candi Déniz, José L Pérez, Antonio Oliver, Ana Mena
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  ABSTRACT: Epidemiological surveillance of Clostridium difficile infection has gained importance in recent years as a result of the rapid spread of epidemic strains, including hypervirulent strains and strains with reduced susceptibility to antimicrobials. The molecular epidemiology and antimicrobial susceptibility of C. difficile in the reference hospital of the Balearic Islands (Spain) is reported in this study. One hundred isolates of toxigenic C. difficile from different patients were selected using rapid dual EIA screening test. All isolates were characterized through toxin profile, PCR ribotyping and, in addition, multi-locus sequence typing (MLST) was performed on fifty selected strains. MICs to metronidazole, vancomycin, erythromycin and moxifloxacin were also determined. A total of 43 different ribotypes were distinguished, with higher prevalence of ribotype 014 (34%). Twenty one per cent of the isolates expressed binary toxin and it is noteworthy that 62% of these were identified as the hypervirulent ribotype 078, the second most prevalent ribotype found in our hospital (13%). A total of 20 different sequence types (STs) were found, including a new described allele and ST. MLST data showed a clear concordance between some ribotypes and STs, mainly represented by ribotype 014/ST-2, ribotype 078/ST-11 and ribotype 001/ST-3. Phylogenetic analysis also revealed that most of the isolates were genetically related, forming a large clonal complex. Finally, ribotypes 078 (ST-11) and 001 (ST-3) were associated with higher resistance to erythromycin and to erythromycin and moxifloxacin, respectively. All these data suggest that the combination of ribotyping and MLST is a good tool for the surveillance of the changing epidemiology of C. difficile. A wide dissemination of clones has been observed in our setting, ribotype 014 (ST-2) being the most prevalent followed by the hypervirulent ribotype 078 (ST-11) and ribotype 001 (ST-3), their spread in our setting probably influenced by their higher resistance.
  International journal of medical microbiology: IJMM 03/2013;
• Article: Community-associated MRSA: What makes them special?

  Michael Otto
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  ABSTRACT: While infections with methicillin-resistant Staphylococcus aureus (MRSA) were traditionally restricted to the hospital setting, novel MRSA strains emerged over the last two decades that have the capacity to infect otherwise healthy people outside of the hospital setting. These community-associated (CA-)MRSA strains combine methicillin resistance with enhanced virulence and fitness. Interestingly, CA-MRSA strains emerged globally and from different backgrounds, indicating that the "trade-off" between maintaining sufficient levels of methicillin resistance and obtaining enhanced virulence at a low fitness cost was achieved on several occasions in convergent evolution. However, frequently this process comprised similar changes. First and foremost, all CA-MRSA strains typically carry a novel type of methicillin resistance locus that appears to cause less of a fitness burden. Additionally, acquisition of specific toxin genes, most notably that encoding Panton-Valentine leukocidin (PVL), and adaptation of gene expression of genome-encoded toxins, such as alpha-toxin and phenol-soluble modulins (PSMs), further contributed to the evolution of CA-MRSA. Finally, the exceptional epidemiological success of the USA300 CA-MRSA clone in particular may have been due to yet another gene acquisition, namely that of the speG gene, which is located on the arginine catabolic mobile element (ACME) and involved in detoxifying harmful host-derived polyamines.
  International journal of medical microbiology: IJMM 03/2013;
• Article: High-resolution typing by MLVF unveils extensive heterogeneity of European livestock-associated methicillin-resistant Staphylococcus aureus isolates with the sequence type 398.

  Corinna Glasner, Artur J Sabat, Monika A Chlebowicz, Wannes Vanderhaeghen, Alexandra Fetsch, Beatriz Guerra, Helen Huber, Roger Stephan, Carmen Torres, Patrick Butaye, Andreas Voss, Mireille Wulf, Jan Maarten van Dijl
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  ABSTRACT: Methicillin-resistant Staphylococcus aureus sequence type 398 (MRSA ST398) has emerged in livestock worldwide. In particular, areas in Europe with high densities of livestock farming are affected. Consequently, the incidence of human colonization and infection with ST398 is rapidly increasing. Distinguishing different ST398 isolates with standard typing tools is problematic. The objective of this study was to examine the discriminatory power of Multiple-Locus Variable number tandem repeat Fingerprinting (MLVF) on a highly diverse ST398 collection. Our data show that MLVF combined with spa-typing is an attractive approach for high-resolution typing of ST398 isolates and unveiling their relatedness.
  International journal of medical microbiology: IJMM 03/2013;
• Article: Antibiotics and antibiotic resistance: A bitter fight against evolution.

  Alexandro Rodríguez-Rojas, Jerónimo Rodríguez-Beltrán, Alejandro Couce, Jesús Blázquez
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  ABSTRACT: One of the most terrible consequences of Darwinian evolution is arguably the emergence and spread of antibiotic resistance, which is becoming a serious menace to modern societies. While spontaneous mutation, recombination and horizontal gene transfer are recognized as the main causes of this notorious phenomenon; recent research has raised awareness that sub-lethal concentrations of antibiotics can also foster resistance as an undesirable side-effect. They can produce genetic changes by different ways, including a raise of free radicals within the cell, induction of error-prone DNA-polymerases mediated by SOS response, imbalanced nucleotide metabolism or affect directly DNA. In addition to certain environmental conditions, subinhibitory concentrations of antimicrobials may increase, even more, the mutagenic effect of antibiotics. Here, we review the state of knowledge on antibiotics as promoters of antibiotic resistance.
  International journal of medical microbiology: IJMM 03/2013;
• Article: Cross-protection provided by live Shigella mutants lacking major antigens.

  Valéria Szijártó, Eva Hunyadi-Gulyás, Levente Emődy, Tibor Pál, Gábor Nagy
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  ABSTRACT: The immune response elicited by Shigella infections is dominated by serotype-specific antibodies recognizing the LPS O-antigens. Although a marked antibody response to invasion plasmid antigens (Ipa-s) shared by all virulent strains is also induced, the varying level of immunity elicited by natural infections is serotype-restricted. Previous vaccines have tried to mimic and achieve this serotype-specific, infection-induced immunity. As, however, the four Shigella species can express 50 different types of O-antigens, current approaches with the aim to induce a broad coverage use a mixture of the most common O-antigens combined in single vaccines. In the current study we present data on an alternative approach to generate immunity protective against multiple serotypes. Mutants lacking both major immune-determinant structures (i.e. the Ipa and O-antigens) were not only highly attenuated, but, unlike their avirulent counterparts still expressing these antigens, elicited a protective immune response to heterologous serotypes in a murine model. Evidence is provided that protection was mediated by the enhanced immunogenic potential of minor conserved antigens. Furthermore, the rough, non-invasive double mutants triggered an immune response different from that induced by the smooth, invasive strains regarding the isotype of antibodies generated. These non-invasive, rough mutants may represent promising candidates for further development into live vaccines for the prophylaxis of bacillary dysentery in areas with multiple endemic serotypes.
  International journal of medical microbiology: IJMM 03/2013;
• Article: Antihypertensives suppress the emergence of fluoroquinolone-resistant mutants in pneumococci: An in vitro study.

  Mathias W Pletz, Nikolay Michaylov, Ulrike Schumacher, Mark van der Linden, Christoph B Duesberg, Thomas Fuehner, Keith P Klugman, Tobias Welte, Oliwia Makarewicz
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  ABSTRACT: BACKGROUND: The antihypertensives reserpine and verapamil are also inhibitors of pneumococcal efflux pumps. We addressed the following questions: (i) Do verapamil and reserpine influence the mutation ratio of pneumococci in the presence of ciprofloxacin? (ii) At which concentrations does this occur? (iii) Is this limited to isolates with efflux phenotype? METHODS: 14 clinical isolates, nested in 6 genetically similar clusters, were used, 7 strains with efflux and 7 without. The mutation ratio in the presence of ciprofloxacin (3×MIC) and increasing concentrations of reserpine and verapamil was determined and the quinolone-resistance determining regions (QRDR) of selected mutants were sequenced. Analysis of the efficacy was performed using a mixed linear model, supported by descriptive statistics. RESULTS: Reserpine and verapamil reduced the mutation ratio of QRDR in the presence of ciprofloxacin with the required concentration for a reduction ≥50% of 1mg/l for reserpine and 50mg/l for verapamil. The mutation prevention effect is not limited to, but is more pronounced in efflux positive phenotypes. CONCLUSION: Reserpine and verapamil can prevent the selection of ciprofloxacin resistant isolates by reduction of the mutation ratio, particularly in strain with an efflux phenotype. However, the required concentrations are too toxic for clinical use.
  International journal of medical microbiology: IJMM 03/2013;
• Article: Hospital-associated MRSA and antibiotic resistance-What have we learned from genomics?

  Jodi A Lindsay
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  ABSTRACT: In many parts of the world, MRSA are responsible for a high proportion of S. aureus infections in patients in contact with healthcare. Molecular studies have shown this is due to one or more MRSA clones that have become endemic in each hospital or healthcare facility, resulting in hospital- or healthcare-associated MRSA (HA-MRSA). The infection rate and clones responsible for HA-MRSA can vary substantially in different geographical locations. Molecular methods have allowed clones to be categorized, as well as the opportunity to track the evolution and spread of clones in healthcare settings and around the world. The genomes of HA-MRSA isolates belonging to the same clonal group can show dramatic variability particularly in the carriage of mobile genetic elements (MGEs) encoding virulence and resistance genes. HA-MRSA are potentially resistant to all classes of antibiotics, although individual isolates that are fully drug resistant are not reported. The incidence of fluoroquinolone resistance in HA-MRSA is remarkably high, suggesting use of this class of antibiotics as well as the β-lactams contributes to the selection and success of HA-MRSA clones in the hospital setting.
  International journal of medical microbiology: IJMM 03/2013;