Regulation of the Staphylococcal Superantigen-Like Protein 1 Gene of Community-Associated Methicillin-Resistant Staphylococcus aureus in Murine Abscesses

Bretl, Daniel J.; Elfessi, Abdulaziz; Watkins, Hannah; Schwan, William R.

doi:10.3390/toxins11070391

Cited by 8 publications

(6 citation statements)

References 63 publications

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“…aureus adherence to and invasion of host cells (8), proteases that modulate the host immune response to the bacterium (9), as well as pore-forming toxins such as alpha toxin and the bicomponent leukocidins that lyse host cells (10). The expression of these various virulence determinants is dependent on factors such as growth rate, the availability of certain nutrients, host interactions, and the presence of antimicrobial compounds (8, 11–13).…”

Section: Introductionmentioning

confidence: 99%

Identification of Key Determinants of Staphylococcus aureus Vaginal Colonization

Deng

Schilcher

Burcham

et al. 2019

mBio

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Staphylococcus 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.

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Section: Introductionmentioning

confidence: 99%

Identification of Key Determinants of Staphylococcus aureus Vaginal Colonization

Deng

Schilcher

Burcham

et al. 2019

mBio

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“…These virulence 72 factors include cell wall-anchored surface proteins that facilitate S. aureus adherence to and 73 invasion of host cells (8), proteases that modulate the host immune response to the bacterium (9), 74 as well as pore-forming toxins such as α-toxin and the bicomponent leukocidins that lyse host 75 cells (10). The expression of these various virulence determinants is dependent on factors such as 76 growth rate, the availability of certain nutrients, host interactions, and the presence of 77 antimicrobial compounds (8,(11)(12)(13). 78 Nasal carriage is known to be a risk factor for S. aureus infections both in the hospital 79 and in the community with individuals often being infected with the strain that they carry (14).…”

Section: Introduction 57mentioning

confidence: 99%

Identification of key determinants ofStaphylococcus aureusvaginal colonization

Deng

Schilcher

Burcham

et al. 2019

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22Staphylococcus aureus is an important pathogen responsible for nosocomial and 23 community acquired infections in humans, and methicillin-resistant S. aureus (MRSA) infections 24 have continued to increase despite wide-spread preventative measures. S. aureus can colonize the 25 female vaginal tract and reports have suggested an increase in MRSA infections in pregnant and 26 postpartum women as well as outbreaks in newborn nurseries. Currently, little is known about 27 specific factors that promote MRSA vaginal colonization and subsequent infection. To study S. 28 aureus colonization of the female reproductive tract in a mammalian system, we developed a 29 mouse model of S. aureus vaginal carriage and demonstrated that both hospital-associated and 30 community-associated MRSA isolates can colonize the murine vaginal tract. 31Immunohistochemical analysis revealed an increase in neutrophils in the vaginal lumen during 32 MRSA colonization. Additionally, we observed that a mutant lacking fibrinogen binding 33 adhesins exhibited decreased persistence within the mouse vagina. To further identify novel 34 factors that promote vaginal colonization, we performed RNA-sequencing to determine the 35 transcriptome of MRSA growing in vivo during vaginal carriage at 5 hours, 1-day, and 3-days 36 post-inoculation. Over 25% of bacterial genes were differentially regulated at all time points 37 during colonization compared to laboratory cultures. The most highly induced genes were those 38 involved in iron acquisition, including the Isd system and siderophore transport systems. Mutants 39 deficient in these pathways did not persist as well during in vivo colonization. These results 40 reveal that fibrinogen binding as well as the capacity to overcome host nutritional limitation are 41 important determinants of MRSA vaginal colonization. 42 43 IMPORTANCE 44Staphylococcus aureus is an opportunistic pathogen able to cause a wide variety of 45 infections in humans. Recent reports have suggested an increasing prevalence of MRSA in 46 pregnant and postpartum women, coinciding with the increased incidence of MRSA infections in 47 the NICU and newborn nurseries. Vertical transmission from mothers to infants at delivery is a 48 likely route of MRSA acquisition by the newborn, however, essentially nothing is known about 49 host and bacterial factors that influence MRSA carriage in the vagina. Here, we established a 50 mouse model of vaginal colonization and observed that multiple MRSA strains can persist in the 51 vaginal tract. Additionally, we determined that MRSA interactions with fibrinogen as well as 52 iron uptake can promote vaginal persistence. This study is the first to identify molecular 53 mechanisms which govern vaginal colonization by MRSA, the critical initial step preceding 54 infection and neonatal transmission. 55 56 treated with 17-estradiol 1-day before inoculation with 10 7 CFU of either USA300 or 131 MRSA252. The next day the vaginal lumen was swabbed and then we euthanized the animals 132 and collected the vagina, c...

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“…A paper by Bretl et al investigated the in vivo regulation of staphylococcal superantigen-like protein 1 [9]. They showed transcription of the ssl1 gene increased when S. aureus was grown under nutrient deprived conditions that included early growth in murine abscesses.…”

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confidence: 99%