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Host- and microbe determinants that may influence the success of S. aureus colonization.

ABSTRACT: Staphylococcus aureus may cause serious skin and soft tissue infections, deep abscesses, endocarditis, osteomyelitis, pneumonia, and sepsis. S. aureus persistently colonizes 25-30% of the adult human population, and S. aureus carriers have an increased risk for infections caused by the bacterium. The major site of colonization is the nose, i.e., the vestibulum nasi, which is covered with ordinary skin and hair follicles. Several host and microbe determinants are assumed to be associated with colonization. These include the presence and expression level of bacterial adhesins, which can adhere to various proteins in the extracellular matrix or on the cellular surface of human skin. The host expresses several antimicrobial peptides and lipids. The level of ?-defensin 3, free sphingosine, and cis-6-hexadecenoic acid are found to be associated with nasal carriage of S. aureus. Other host factors are certain polymorphisms in Toll-like receptor 2, mannose-binding lectin, C-reactive protein, glucocorticoid-, and vitamin D receptor. Additional putative determinants for carriage include genetic variation and expression of microbial surface components recognizing adhesive matrix molecules and their interaction partners, as well as variation among humans in the ability of recognizing and responding appropriately to the bacteria. Moreover, the available microflora may influence the success of S. aureus colonization. In conclusion, colonization is a complex interplay between the bacteria and its host. Several bacterial and host factors are involved, and an increased molecular understanding of these are needed.

SUBMITTER: Johannessen M

PROVIDER: S-EPMC3417514 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Host- and microbe determinants that may influence the success of S. aureus colonization.

Johannessen Mona M Sollid Johanna E JE Hanssen Anne-Merethe AM

Frontiers in cellular and infection microbiology 20120504

Staphylococcus aureus may cause serious skin and soft tissue infections, deep abscesses, endocarditis, osteomyelitis, pneumonia, and sepsis. S. aureus persistently colonizes 25-30% of the adult human population, and S. aureus carriers have an increased risk for infections caused by the bacterium. The major site of colonization is the nose, i.e., the vestibulum nasi, which is covered with ordinary skin and hair follicles. Several host and microbe determinants are assumed to be associated with col ...[more]

PMID: 22919647

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Project description:Staphylococcus aureus is an important pathogen responsible for nosocomial and community-acquired infections in humans, and methicillin-resistant S. aureus (MRSA) infections have continued to increase despite widespread preventative measures. S. aureus can colonize the female vaginal tract, and reports have suggested an increase in MRSA infections in pregnant and postpartum women as well as outbreaks in newborn nurseries. Currently, little is known about specific factors that promote MRSA vaginal colonization and subsequent infection. To study S. aureus colonization of the female reproductive tract in a mammalian system, we developed a mouse model of S. aureus vaginal carriage and demonstrated that both hospital-associated and community-associated MRSA isolates can colonize the murine vaginal tract. Immunohistochemical analysis revealed an increase in neutrophils in the vaginal lumen during MRSA colonization. Additionally, we observed that a mutant lacking fibrinogen binding adhesins exhibited decreased persistence within the mouse vagina. To further identify novel factors that promote vaginal colonization, we performed RNA sequencing to determine the transcriptome of MRSA growing in vivo during vaginal carriage at 5 h, 1 day, and 3 days postinoculation. Over 25% of the bacterial genes were differentially regulated at all time points during colonization compared to laboratory cultures. The most highly induced genes were those involved in iron acquisition, including the Isd system and siderophore transport systems. Mutants deficient in these pathways did not persist as well during in vivo colonization. These results reveal that fibrinogen binding and the capacity to overcome host nutritional limitation are important determinants of MRSA vaginal colonization.IMPORTANCEStaphylococcus aureus is an opportunistic pathogen able to cause a wide variety of infections in humans. Recent reports have suggested an increasing prevalence of MRSA in pregnant and postpartum women, coinciding with the increased incidence of MRSA infections in neonatal intensive care units (NICUs) and newborn nurseries. Vertical transmission from mothers to infants at delivery is a likely route of MRSA acquisition by the newborn; however, essentially nothing is known about host and bacterial factors that influence MRSA carriage in the vagina. Here, we established a mouse model of vaginal colonization and observed that multiple MRSA strains can persist in the vaginal tract. Additionally, we determined that MRSA interactions with fibrinogen and iron uptake can promote vaginal persistence. This study is the first to identify molecular mechanisms which govern vaginal colonization by MRSA, the critical initial step preceding infection and neonatal transmission.

Project description:BACKGROUND:The proportion of blood meals that mosquitoes take from a host species is a function of the interplay of extrinsic (abundance and location of potential hosts) and intrinsic (innate preference) factors. A mark-release-recapture experiment addressed whether host preference in a population of Anopheles farauti was uniform or if there were anthropophilic and zoophilic subpopulations. The corresponding fitness associated with selecting different hosts for blood meals was compared by measuring fecundity. METHODS:The attractiveness of humans for blood meals by An. farauti in the Solomon Islands was compared to pigs using tent traps. Host fidelity was assessed by mark-release-recapture experiments in which different colour dusts were linked to the host to which the mosquito was first attracted. Outdoor resting An. farauti were captured on barrier screens and the human blood index (HBI) as well as the feeding index were calculated. The fecundity of individual An. farauti after feeding on either humans or pigs was assessed from blood-fed mosquitoes held in individual oviposition chambers. RESULTS:Anopheles farauti were more attracted to humans than pigs at a ratio of 1.31:1.00. The mark-release-recapture experiment found evidence for An. farauti being a single population regarding host preference. The HBI of outdoor resting An. farauti was 0.93 and the feeding index was 1.29. Anopheles farauti that fed on a human host laid more eggs but had a longer oviposition time compared to An. farauti that had blood fed on a pig. CONCLUSIONS:One of the strongest drivers for host species preference was the relative abundance of the different host species. Here, An. farauti have a slight preference for humans over pigs as blood meal sources. However, the limited availability of alternative hosts relative to humans in the Solomon Islands ensures a very high proportion of blood meals are obtained from humans, and thus, the transmission potential of malaria by An. farauti is high.

Project description:UNLABELLED:Staphylococcus aureus is a Gram-positive, commensal bacterium known to asymptomatically colonize the human skin, nares, and gastrointestinal tract. Colonized individuals are at increased risk for developing S. aureus infections, which range from mild skin and soft tissue infections to more severe diseases, such as endocarditis, bacteremia, sepsis, and osteomyelitis. Different virulence factors are required for S. aureus to infect different body sites. In this study, virulence gene expression was analyzed in two S. aureus isolates during nasal colonization, bacteremia and in the heart during sepsis. These models were chosen to represent the stepwise progression of S. aureus from an asymptomatic colonizer to an invasive pathogen. Expression of 23 putative S. aureus virulence determinants, representing protein and carbohydrate adhesins, secreted toxins, and proteins involved in metal cation acquisition and immune evasion were analyzed. Consistent upregulation of sdrC, fnbA, fhuD, sstD, and hla was observed in the shift between colonization and invasive pathogen, suggesting a prominent role for these genes in staphylococcal pathogenesis. Finally, gene expression data were correlated to the roles of the genes in pathogenesis by using knockout mutants in the animal models. These results provide insights into how S. aureus modifies virulence gene expression between commensal and invasive pathogens. IMPORTANCE:Many bacteria, such as Staphylococcus aureus, asymptomatically colonize human skin and nasal passages but can also cause invasive diseases, such as bacteremia, pneumonia, sepsis, and osteomyelitis. The goal of this study was to analyze differences in the expression of selected S. aureus genes during a commensal lifestyle and as an invasive pathogen to gain insight into the commensal-to-pathogen transition and how a bacterial pathogen adapts to different environments within a host (e.g., from nasal colonization to invasive pathogen). The gene expression data were also used to select genes for which to construct knockout mutants to assess the role of several proteins in nasal colonization and lethal bacteremia. These results not only provide insight into the factors involved in S. aureus disease pathogenesis but also provide potential therapeutic targets.

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Host- and microbe determinants that may influence the success of S. aureus colonization.

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Host- and microbe determinants that may influence the success of S. aureus colonization.

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