The Identification of Genetic Factors Influencing Susceptibility to Staphylococcus aureus Infection in mice susceptible and resistant to S. aureus infection
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE23584 | GEO | 2011/12/31
SECONDARY ACCESSION(S): PRJNA131837
REPOSITORIES: GEO
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Project description:It has been shown that inbred strains of mice exhibit variable susceptibility to S. aureus infection, but the specific genes responsible for this differential phenotype are unknown. Using ISHM to identify genomic regions associated with the phenotypes, we considered genes within those interval to be candidate genes and used the gene expression patterns of the genes contained in the region to determine whether the genes are differentially expressed between the 2 phenotypically different groups of mice. To identify genes differentially expressed between mice susceptible and resistant to S. aureus infection that could contribute to host susceptibility to S. aureus infection, we compared the gene expression profiles between 2 groups of mice where 3 were susceptible (A/J, BALBcBy/J, AKR/J) and resistant (C57BL/J, C3H/HeJ, NOD/ShiLtJ) to S. aureus. The susceptible group had high bacterial count values in the kidney while the resistant group had low values.
2011-12-31 | E-GEOD-23584 | biostudies-arrayexpress
Project description:ObjectivesIn vitro trends of cefazolin and ceftriaxone susceptibilities from pediatric clinical isolates of methicillin-susceptible Staphylococcus aureus (MSSA) between 2011 and 2016 were analyzed for surveillance.MethodsOur laboratory continues to use agar disk diffusion for staphylococcal susceptibilities applying Clinical Laboratory Standard Institute's 2012 breakpoints.ResultsA total of 3992 MSSA clinical isolates in the last 6 years were analyzed for their in vitro cefazolin and ceftriaxone susceptibilities. While all MSSA isolates exhibited cefazolin susceptibilities within the "susceptible" zone range, there have been a proportion of isolates with ceftriaxone susceptibilities falling in "intermediate" zones, ranging from 2.6% in 2011 to 8.3% in 2016.ConclusionsCefazolin continues to be the recommended agent for MSSA treatment at our institution, reflected by the finding that only 2% (6/321) of patients who received ceftriaxone as definitive therapy for MSSA bacteremia during the study period. We have confirmed the cefoxitin-predicted MSSA susceptibility to cefazolin, but have found concerning drifts in ceftriaxone susceptibilities by continued in vitro monitoring over the last 6 years.
| S-EPMC5819674 | biostudies-literature
Project description:Genes Influencing Susceptibility to Infection and Malnutrition
| PRJNA416030 | ENA
Project description:Genes Influencing Susceptibility to Infection and Malnutrition
| PRJNA416029 | ENA
Project description:We report characterization of a methicillin-susceptible, vancomycin-resistant bloodstream isolate of Staphylococcus aureus recovered from a patient in Brazil. Emergence of vancomycin resistance in methicillin-susceptible S. aureus would indicate that this resistance trait might be poised to disseminate more rapidly among S. aureus and represents a major public health threat.
| S-EPMC4593430 | biostudies-literature
Project description:Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that factors on chromosomes (chr) 8, 11, and 18 are responsible for susceptibility to S. aureus sepsis in A/J mice. F1 mice from C57BL/6J X CSS8 cross (C8A) and C57BL/6J X CSS18 (C18A) were also susceptible to S. aureus (median survival < 48 h), whereas F1 mice from C57BL/6J X CSS11 cross (C11A) were resistant (median survival > 120 h) to S. aureus. Bacterial loads in the kidney were consistent with F1 median survivals, with higher bacterial counts in susceptible mice. No sexlinked associations with susceptibility were noted in F1 intercrosses. Using whole genome transcription profiling, we identified a total of 192 genes on chromosomes 8, 11, and 18 which are differentially expressed between A/J and C57BL/6J in the setting of S. aureus infection. Of these, 28 genes had Gene Ontology annotations indicating a potential immune response function. These 28 genes are associated with susceptibility to S. aureus in A/J mice, and are potential determinants of susceptibility to S. aureus infection in humans.
2010-08-01 | GSE19668 | GEO
Project description:Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that factors on chromosomes (chr) 8, 11, and 18 are responsible for susceptibility to S. aureus sepsis in A/J mice. F1 mice from C57BL/6J X CSS8 cross (C8A) and C57BL/6J X CSS18 (C18A) were also susceptible to S. aureus (median survival < 48 h), whereas F1 mice from C57BL/6J X CSS11 cross (C11A) were resistant (median survival > 120 h) to S. aureus. Bacterial loads in the kidney were consistent with F1 median survivals, with higher bacterial counts in susceptible mice. No sexlinked associations with susceptibility were noted in F1 intercrosses. Using whole genome transcription profiling, we identified a total of 192 genes on chromosomes 8, 11, and 18 which are differentially expressed between A/J and C57BL/6J in the setting of S. aureus infection. Of these, 28 genes had Gene Ontology annotations indicating a potential immune response function. These 28 genes are associated with susceptibility to S. aureus in A/J mice, and are potential determinants of susceptibility to S. aureus infection in humans. To identify genes for which differential expression between A/J and C57BL/6J mice could contribute to host susceptibility to S. aureus infection, we compared the gene expression profiles between uninfected A/J and C57BL/6J mice and between infected A/J and C57BL/6J mice at 2, 4, 6, and 12 hours after infection.
2010-08-01 | E-GEOD-19668 | biostudies-arrayexpress
Project description:Few studies have been conducted on the susceptibility of bacteria to biocides. A total of 182 methicillin-resistant and -susceptible Staphylococcus aureus isolates collected from healthy or diseased humans and animals in Germany were included in the present study. Sixty-three isolates of animal origin and 119 human isolates were tested for their MICs to eight biocides or heavy metals by the broth microdilution method. The MIC50 and MIC90 values of human and animal isolates were equal or differed by not more than 1 dilution step, and statistical analysis revealed that differences between MICs of human and animal isolates were not significant. However, when taking into account the multilocus sequence type (MLST), a strong tendency (P = 0.054) to higher MICs of silver nitrate was detected for clonal complex 398 (CC398) isolates from humans compared to those from animals. Furthermore, a comparison of MIC values from isolates belonging to different clonal lineages revealed that important human lineages such as CC22 and CC5 exhibited significantly (P < 0.05) higher MICs for the biocides chlorhexidine, benzethonium chloride, and acriflavine than the main animal lineage sequence type 398 (ST398). Isolates with elevated MIC values were tested for the presence of biocide and heavy metal tolerance-mediating genes by PCR assays, and the following genes were detected: mepA (n [no. of isolates containing the gene] = 44), lmrS (n = 36), norA (n = 35), sepA (n = 22), mco (n = 5), czrC (n = 3), smr (n = 2), copA (n = 1), qacA and/or -B (n = 1), qacG (n = 2), and qacJ (n = 1). However, only for some compounds was a correlation between the presence of a biocide tolerance gene and the level of MIC values detected.IMPORTANCE Biocides play an essential role in controlling the growth of microorganisms and the dissemination of nosocomial pathogens. In this study, we determined the susceptibility of methicillin-resistant and -susceptible S. aureus isolates from humans and animals to various biocides and heavy metal ions and analyzed differences in susceptibilities between important clonal lineages. In addition, the presence of biocide or heavy metal tolerance-mediating genes was investigated. We demonstrated that important human lineages such as CC22 and CC5 had significantly higher MIC values for chlorhexidine, benzethonium chloride, and acriflavine than the main farm animal lineage, ST398. In addition, it was shown that for some combinations of biocides and tolerance genes, significantly higher MICs were detected for carriers. These findings provide new insights into S. aureus biocide and heavy metal tolerance.
| S-EPMC6007098 | biostudies-literature
Project description:Staphylococcus aureus is a human commensal that can also cause systemic infections. This transition requires evasion of the immune response and the ability to exploit different niches within the host. However, the disease mechanisms and the dominant immune mediators against infection are poorly understood. Previously it has been shown that the infecting S. aureus population goes through a population bottleneck, from which very few bacteria escape to establish the abscesses that are characteristic of many infections. Here we examine the host factors underlying the population bottleneck and subsequent clonal expansion in S. aureus infection models, to identify underpinning principles of infection. The bottleneck is a common feature between models and is independent of S. aureus strain. Interestingly, the high doses of S. aureus required for the widely used "survival" model results in a reduced population bottleneck, suggesting that host defences have been simply overloaded. This brings into question the applicability of the survival model. Depletion of immune mediators revealed key breakpoints and the dynamics of systemic infection. Loss of macrophages, including the liver Kupffer cells, led to increased sensitivity to infection as expected but also loss of the population bottleneck and the spread to other organs still occurred. Conversely, neutrophil depletion led to greater susceptibility to disease but with a concomitant maintenance of the bottleneck and lack of systemic spread. We also used a novel microscopy approach to examine abscess architecture and distribution within organs. From these observations we developed a conceptual model for S. aureus disease from initial infection to mature abscess. This work highlights the need to understand the complexities of the infectious process to be able to assign functions for host and bacterial components, and why S. aureus disease requires a seemingly high infectious dose and how interventions such as a vaccine may be more rationally developed.
| S-EPMC6019756 | biostudies-literature
Project description:ImportanceStaphylococcus aureus is one of the leading causes of infections in neonatal intensive care units (NICUs). Most studies in this patient group focus on methicillin-resistant S aureus or the outbreak setting, whereas data for methicillin-susceptible S aureus are limited.ObjectivesTo identify risk factors for S aureus colonization and infections in hospitalized newborns and to investigate S aureus transmission and its dynamics in a nonoutbreak setting.Design, setting, and participantsThis monocentric cohort study in a tertiary NICU in Heidelberg, Germany, enrolled all hospitalized neonates (n = 590) with at least 1 nasal screening swab positive for S aureus. Data were collected from January 1, 2018, to December 31, 2019.ExposuresWeekly screening for S aureus colonization was performed for all newborns until discharge.Main outcomes and measuresThe primary end point was any S aureus infection until hospital discharge. Transmission of S aureus and performance of routine typing to detect transmissions were defined as the secondary outcomes of the study.ResultsIn total, 590 newborns were enrolled (276 [46.8%] female and 314 [53.2%] male; 220 [37.3%] with birthweight <1500 g; 477 [80.8%] preterm; 449 [76.1%] singletons; 419 [71.5%] delivered via cesarean section). The median length of stay was 26 (range, 10-62) days. Overall, 135 infants (22.9%) were colonized by S aureus at some time during their hospital stay. The median time to first detection was 17 (interquartile range, 11-37) days. The overall incidence of S aureus infection was 1.7% (10 of 590). Low birth weight (<1500 g [odds ratio, 9.3; 95% CI, 5.9-14.6; P < .001]) and longer hospital stay (odds ratio, 2.3; 95% CI, 1.9-2.7; P < .001) were associated with colonization. Nasal carriage was significantly associated with S aureus infection (odds ratio, 8.2; 95% CI, 2.1-32.3; P = .002). A total of 123 of 135 colonization isolates were sequenced. All recoverable infection isolates (4 of 7) of newborns with colonization were genetically identical to the colonizing isolate. Whole-genome sequencing indicated 23 potential transmission clusters.Conclusions and relevanceThe findings of this cohort study suggest that nasal colonization is a relevant risk factor for S aureus infection in a nonoutbreak NICU setting. In colonized newborns, infection and colonization isolates were genetically identical, suggesting that eradication of colonization may be a useful measure to prevent infection. Further investigations are necessary to validate and assess the generalizability of our findings.
| S-EPMC8438598 | biostudies-literature