How Staphylococcus aureus adapts to its host.

Columbia University College of Physicians and Surgeons, New York, USA.
New England Journal of Medicine (Impact Factor: 54.42). 05/2011; 364(21):1987-90. DOI: 10.1056/NEJMp1100251
Source: PubMed
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    ABSTRACT: Strains of Staphylococcus aureus with an intermediate level of resistance to vancomycin (vancomycin-intermediate S. aureus, or VISA) or which contain subpopulations of mixed susceptibility (heterogeneous VISA, or hVISA) have been reported worldwide. However, the prevalence of VISA and hVISA infections in Northeast China is unknown. From 2007 through 2010, we surveyed the vancomycin susceptibility of methicillin-resistant and methicillin-sensitive S. aureus (MRSA and MSSA, respectively) clinical isolates in Northeast China. S. aureus clinical isolates (369 MRSA and 388 MSSA) were screened for hVISA and VISA on brain heart infusion agar containing 3 μg/mL vancomycin, and their identity confirmed using a modified population analysis profile-area under the curve method and broth microdilution. All hVISA and VISA isolates were characterized genotypically and phenotypically. Ten percent and 0.5 percent of the isolates were hVISA and VISA, respectively. The proportion of hVISA among MSSA isolates for the entire study period was 4.1%, but increased significantly year-by-year, from 1.2% in 2007 to 7.2% in 2010. The predominant sources of hVISA and VISA isolates were sputum (56.3%), pus (18.8%), and blood (8.8%). Molecular typing of hVISA and VISA strains revealed that, taken together, 80% contained the accessory gene regulator (agr) group II, and of these, 85.7% of the MR-hVISA and MR-VISA strains were staphylococcal cassette chromosome mec (SCCmec) type II. The adherence ability of all hVISA and VISA strains was reduced compared with that of vancomycin-susceptible strains, shown by biofilm assay. The percentage of hVISA strains was high and increased each year. The proportion of hVISA among MSSA specifically also increased significantly each year. In isolates collected from diverse infection sites, hVISA and VISA strains were found predominantly in sputum, pus, and blood, in descending order. Testing for vancomycin susceptibility should include both MRSA and MSSA isolates collected from different clinical sites.
    PLoS ONE 09/2013; 8(9):e73300. DOI:10.1371/journal.pone.0073300 · 3.53 Impact Factor
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    ABSTRACT: Near transporter (NEAT) domains of the iron-regulated surface determinant (Isd) proteins are essential for the import of nutritional heme from host animals to Gram-positive pathogens such as Staphylococcus aureus. The order of transfer of heme between NEAT domains occurs from IsdH to IsdA to IsdC, without any energy input despite the similarity of their three-dimensional structures. We measured the free energy of binding of heme and various metalloporphyrins to each NEAT domain and found that the affinity of heme and non-iron porphyrins for NEAT domains increased gradually in the same order as that for heme transfer. To gain insight into the atomistic mechanism for the differential affinities, we performed in silico molecular dynamics simulation and in vitro site-directed mutagenesis. The simulations revealed that the negatively charged residues that are abundant in the loop between strand β1b and the 310 helix of IsdH-NEAT3 destabilize the interaction with the propionate group of heme. The higher affinity of IsdC was in part attributed to the formation of a salt bridge between its unique residue, Glu88, and the conserved Arg100 upon binding to heme. In addition, we found that Phe130 of IsdC makes the β7−β8 hairpin less flexible in the ligand-free form, which serves to reduce the magnitude of the entropy loss on binding to heme. We confirmed that substitution of these key residues of IsdC decreased its affinity for heme. Furthermore, IsdC mutants, whose affinities for heme were lower than those of IsdA, transferred heme back to IsdA. Thus, NEAT domains have evolved the characteristic residues on the common structural scaffold such that they exhibit different affinities for heme, thus promoting the efficient transfer of heme.
    Biochemistry 11/2013; 52(49):8866–8877. DOI:10.1021/bi4008325 · 3.38 Impact Factor
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    ABSTRACT: BackgroundThe purpose of this study was to identify potential predisposing factors associated with human infectious mastitis.MethodsWe conducted a case–control study among breastfeeding women, with 368 cases (women with mastitis) and 148 controls. Data were collected by a questionnaire designed to obtain retrospective information about several factors related to medical history of mother and infant, different aspects of pregnancy, delivery and postpartum, and breastfeeding practices that could be involved in mastitis. Bivariate analyses and multivariate logistic regression model were used to examine the relationship between mastitis and these factors.ResultsThe variables significantly- and independently-associated with mastitis were cracked nipples (P < 0.0001), oral antibiotics during breastfeeding (P < 0.0001), breast pumps (P < 0.0001), topical antifungal medication during breastfeeding (P = 0.0009), mastitis in previous lactations (P = 0.0014), breast milk coming in later than 24 h postpartum (P = 0.0016), history of mastitis in the family (P = 0.0028), mother-infant separation longer than 24 h (P = 0.0027), cream on nipples (P = 0.0228) and throat infection (P = 0.0224).ConclusionsValuable factors related to an increased risk of infectious mastitis have been identified. This knowledge will allow practitioners to provide appropriate management advice about modifiable risk factors, such as the use of pumps or inappropriate medication. They also could identify before delivery those women at an increased risk of developing mastitis, such as those having a familial history of mastitis, and thus develop strategies to prevent this condition.
    BMC Pregnancy and Childbirth 06/2014; 14(1):195. DOI:10.1186/1471-2393-14-195 · 2.15 Impact Factor