Genome-Wide Association Study of Staphylococcus aureus Carriage in a Community-Based Sample of Mexican-Americans in Starr County, Texas.
ABSTRACT: Staphylococcus aureus is the number one cause of hospital-acquired infections. Understanding host pathogen interactions is paramount to the development of more effective treatment and prevention strategies. Therefore, whole exome sequence and chip-based genotype data were used to conduct rare variant and genome-wide association analyses in a Mexican-American cohort from Starr County, Texas to identify genes and variants associated with S. aureus nasal carriage. Unlike most studies of S. aureus that are based on hospitalized populations, this study used a representative community sample. Two nasal swabs were collected from participants (n = 858) 11-17 days apart between October 2009 and December 2013, screened for the presence of S. aureus, and then classified as either persistent, intermittent, or non-carriers. The chip-based and exome sequence-based single variant association analyses identified 1 genome-wide significant region (KAT2B) for intermittent and 11 regions suggestively associated with persistent or intermittent S. aureus carriage. We also report top findings from gene-based burden analyses of rare functional variation. Notably, we observed marked differences between signals associated with persistent and intermittent carriage. In single variant analyses of persistent carriage, 7 of 9 genes in suggestively associated regions and all 5 top gene-based findings are associated with cell growth or tight junction integrity or are structural constituents of the cytoskeleton, suggesting that variation in genes associated with persistent carriage impact cellular integrity and morphology.
Project description:Staphylococcus aureus (S. aureus) colonizes the anterior nares in part of the population and the persistent carrier state is associated with increased infection risk. Knowledge concerning the determinants of S. aureus nasal carriage is limited. Previously, we found that glucocorticoid receptor polymorphisms influence carrier risk, suggesting involvement of glucocorticoids. Our aim was to study long-term cortisol levels in non-carriers, intermittent, and persistent carriers of S. aureus. We hypothesized that cortisol levels are higher in carriers, since cortisol-induced immune suppression would enhance S. aureus colonization. We determined nasal carrier state and long-term hair cortisol levels in 72 healthy subjects. Nasal swabs were collected twice with an interval of 2 weeks. Cortisol levels were determined in hair segments of 3 cm, which corresponds to a period of roughly 3 months. Of all 72 participants, 38 were non-carriers, 10 were intermittent carriers, and 24 were persistent carriers of S. aureus. Cortisol levels did not differ between these carrier groups (p=0.638). Long-term cortisol levels are not associated with S. aureus nasal carriage.
Project description:Background: The anterior nares are the main ecological niche for Staphylococcus aureus, an important commensal and opportunistic pathogen. Medical students are frequently colonized by a variety of pathogens. Microbial interactions in the human nose can prevent or favor colonization by pathogens, and individuals colonized by pathogens have increased risk of infection and are the source of transmission to other community members or susceptible individuals. According to recent studies, the microbiome from several anatomic areas of healthy individuals varies across different ethnicities. Although previous studies analyzed the nasal microbiome in association with S. aureus carriage, those studies did not provide information regarding ethnicity of participants. Our aim was to assess S. aureus nasal carriage patterns and prevalence among medical students from Colombia, a country of Hispanic origin, and to investigate possible associations of colonization and nasal microbiome composition (bacterial and fungal) in a subgroup of students with known S. aureus carriage patterns. Methods: Nasal swabs from second-year medical students were used to determine prevalence and patterns of S. aureus nasal carriage. Based on microbiological results, we assigned participants into one of three patterns of S. aureus colonization: persistent, intermittent, and non-carrier. Then, we evaluated the composition of nasal microbial communities (bacterial and fungal) in 5 individuals from each carriage category using 16S rRNA and Internal-Transcribed-Spacer sequencing. Results: Prevalence of S. aureus nasal carriage among medical students was 28%. Carriage of methicillin-resistant strains was 8.4% and of methicillin-sensitive strains was 19.6%. We identified 19.6% persistent carriers, 17.5% intermittent carriers, and 62.9% non-carriers. Conclusions: Analysis of nasal microbiome found that bacterial and fungal diversity was higher in individuals colonized by S. aureus than in non-carriers; however, the difference among the three groups was non-significant. We confirmed that fungi were present within the healthy anterior nares at substantial biomass and richness.
Project description:Staphylococcus aureus (SA) nasal colonization plays a critical role in the pathogenesis of staphylococcal infections and SA eradication from the nares has proven to be effective in reducing endogenous infections. To understand SA nasal colonization and its relation with consequent disease, assessment of nasal carriage dynamics and genotypic diversity among a diverse population is a necessity.We have performed extensive longitudinal monitoring of SA nasal carriage isolates in 109 healthy individuals over a period of up to three years. Longitudinal sampling revealed that 24% of the individuals were persistent SA nasal carriers while 32% were intermittent. To assess the genetic relatedness between different SA isolates within our cohort, multi locus sequence typing (MLST) was performed. MLST revealed that not only were strains colonizing intermittent and persistent nasal carriers genetically similar, belonging to the same clonal complexes, but strain changes within the same host were also observed over time for both types of carriers. More highly discriminating genetic analyses using the hypervariable regions of staphylococcal protein A and clumping factor B virulence genes revealed no preferential colonization of specific SA strains in persistent or intermittent carriers. Moreover, we observed that a subset of persistent and intermittent carriers retained clinically relevant community-acquired methicillin-resistant SA (CA-MRSA) strains in their nares over time.The findings of this study provides added perspective on the nasal carriage dynamics between strains colonizing persistent and intermittent carriers; an area currently in need of assessment given that persistent carriers are at greater risk of autoinfection than intermittent carriers.
Project description:This study aimed to evaluate the persistence of nasal carriage of Staphylococcus aureus, methicillin-resistant S. aureus and multidrug-resistant S. aureus over 14?days of follow-up among industrial hog operation workers in North Carolina.Workers anticipating at least 24?h away from work were enrolled June-August 2012. Participants self-collected a nasal swab and completed a study journal on the evening of day 1, and each morning and evening on days 2-7 and 14 of the study. S. aureus isolated from nasal swabs were assessed for antibiotic susceptibility, spa type and absence of the scn gene. Livestock association was defined by absence of scn.Twenty-two workers provided 327 samples. S. aureus carriage end points did not change with time away from work (mean 49?h; range >0-96?h). Ten workers were persistent and six were intermittent carriers of livestock-associated S. aureus. Six workers were persistent and three intermittent carriers of livestock-associated multidrug-resistant S. aureus. One worker persistently carried livestock-associated methicillin-resistant S. aureus. Six workers were non-carriers of livestock-associated S. aureus. Eighty-two per cent of livestock-associated S. aureus demonstrated resistance to tetracycline. A majority of livestock-associated S. aureus isolates (n=169) were CC398 (68%) while 31% were CC9. No CC398 and one CC9 isolate was detected among scn-positive isolates.Nasal carriage of livestock-associated S. aureus, multidrug-resistant S. aureus and methicillin-resistant S. aureus can persist among industrial hog operation workers over a 14-day period, which included up to 96?h away from work.
Project description:Previous research on Staphylococcus aureus in pigs focused on livestock-associated methicillin-resistant S. aureus (MRSA) and had a qualitative cross-sectional design. This study aimed to elucidate the frequency, load, and stability of S. aureus nasal carriage in pigs over time and investigated possible associations between carriage and immune response. Nasal swabs were collected three times weekly from 480 tagged adult pigs in 20 Danish production farms. S. aureus and MRSA were quantified on selective media by the most-probable-number method. The levels of IgG against 10 S. aureus antigens in serum were quantified in selected pigs by a Luminex assay. All the farms were positive for S. aureus and 15 for MRSA, leading to overall prevalences of persistent and intermittent carriers and noncarriers of 24, 52, and 23%, respectively. Carriage frequency and nasal loads were significantly higher on MRSA-positive farms. Logistic-regression modeling revealed the presence of individual pigs characterized by high nasal loads (>10,000 CFU per swab) and stable carriage regardless of farm- and pen-associated factors. On the other hand, the humoral response was strongly influenced by these environmental factors. The existence of a minority of shedders contributing to maintenance of S. aureus within farms opens up new perspectives on the control of MRSA in pig farming.
Project description:<h4>Objective</h4>Staphylococcus aureus is a major human pathogen, and nasal carriers have an increased risk for infection and disease. The exploration of host determinants for nasal carriage is relevant to decrease infection burden. Former studies demonstrate lower carriage prevalence in women and among users of progestin-only contraceptives. The aim of this study was to investigate the possible associations between circulating sex-steroid hormones and nasal carriage of Staphylococcus aureus in a general population.<h4>Methods</h4>In the population-based sixth Tromsø study (2007-2008) nurses collected nasal swab samples from 724 women aged 30-87 not using any exogenous hormones, and 700 of the women had a repeated nasal swab taken (median interval 28 days). We analysed a panel of serum sex-steroids by liquid chromatography tandem mass spectrometry, and collected information about lifestyle, health and anthropometric measures. Multivariable logistic regression was used to study the association between circulating sex-steroids and Staphylococcus aureus carriage (one swab) and persistent carriage (two swabs), while adjusting for potential confounding factors. Women in luteal phase were excluded in the analysis of androgens.<h4>Results</h4>Staphylococcus aureus persistent nasal carriage prevalence was 22%. One standard deviation increase in testosterone and bioavailable testosterone was associated with lower odds of persistent nasal carriage, (OR = 0.57; 95% CI = 0.35-0.92 and OR = 0.52, 95% CI = 0.30-0.92) respectively. Analysis stratified by menopause gave similar findings. Persistent carriers had lower average levels of androstenedione and DHEA, however, not statistically significant.<h4>Conclusion</h4>This large population-based study supports that women with lower levels of circulating testosterone may have increased probability of Staphylococcus aureus persistent carriage.
Project description:Athletes have a higher risk of infection with Staphylococcus aureus than the general population. Most studies in athletes have included primarily male contact sports participants and have not assessed S. aureus carriage over time. We aimed to examine the epidemiology and risk factors of S. aureus carriage in a cohort of male and female collegiate athletes.We conducted a prospective cohort study of 377 varsity collegiate athletes from August 2008 to April 2010. A baseline questionnaire ascertained risk factors for colonization. Nasal and oropharyngeal swabs were obtained at enrollment and monthly thereafter to detect S. aureus colonization. The primary outcome was S. aureus colonization, both with methicillin-susceptible and methicillin-resistant S. aureus, as defined by bacterial culture and molecular confirmation. Secondary outcomes were time to colonization with S. aureus and carriage profile, defined as non-carrier, intermittent carrier, or persistent carrier.Overall, 224 contact sports and 153 non-contact sports athletes were enrolled. Contact sports athletes had a higher risk of carrying S. aureus over time: They had higher odds of being colonized with MRSA (OR 2.36; 95 % CI 1.13-4.93) and they tended to carry S. aureus for longer periods of time (intermittent carriage OR 3.60; 95 % CI 2.02-6.40; persistent carriage OR 2.39; 95 % CI 1.21-4.72). Athletes engaged in contact sports also acquired S. aureus more quickly (HR 1.61; 95 % CI 1.02-2.55).Staphylococcus aureus carriage was common in contact sports athletes. These findings suggest that efforts to prevent transmission of S. aureus among athletes should be focused on contact sports teams.
Project description:Staphylococcus aureus nasal carriage increases infection risk. However, few studies have investigated S. aureus acquisition/loss over >1 year, and fewer still used molecular typing.1123 adults attending five Oxfordshire general practices had nasal swabs taken. 571 were re-swabbed after one month then every two months for median two years. All S. aureus isolates were spa-typed. Risk factors were collected from interviews and medical records.32% carried S. aureus at recruitment (<1% MRSA). Rates of spa-type acquisition were similar in participants S. aureus positive (1.4%/month) and negative (1.8%/month, P = 0.13) at recruitment. Rates were faster in those carrying clonal complex (CC)15 (adjusted (a)P = 0.03) or CC8 (including USA300) (aP = 0.001) at recruitment versus other CCs. 157/274 (57%) participants S. aureus positive at recruitment returning ? 12 swabs carried S. aureus consistently, of whom 135 carried the same spa-type. CC22 (including EMRSA-15) was more prevalent in long-term than intermittent spa-type carriers (aP = 0.03). Antibiotics transiently reduced carriage, but no other modifiable risk factors were found.Both transient and longer-term carriage exist; however, the approximately constant rates of S. aureus gain and loss suggest that 'never' or truly 'persistent' carriage are rare. Long-term carriage varies by strain, offering new explanations for the success of certain S. aureus clones.
Project description:The natural history of contemporary Staphylococcus aureus nasal colonization was evaluated in community children during a 1-year period. Methicillin-susceptible S. aureus nasal carriage was more persistent than methicillin-resistant S. aureus nasal carriage, which was usually self-limited. Children with persistent staphylococcal colonization often carried identical strains. Identification of persistent methicillin-resistant S. aureus carriers might inform strategies for decolonization and reduction of staphylococcal transmission.
Project description:Carriage of Staphylococcus aureus is a risk for infections. Targeted decolonization reduces postoperative infections but depends on accurate screening.To compare detection of S. aureus carriage in healthy individuals between anatomical sites and nurse- versus self-swabbing; also to determine whether a single nasal swab predicted carriage over four weeks.Healthy individuals were recruited via general practices. After consent, nurses performed multi-site swabbing (nose, throat, and axilla). Participants performed nasal swabbing twice-weekly for four weeks. Swabs were returned by mail and cultured for S. aureus. All S. aureus isolates underwent spa typing. Persistent carriage in individuals returning more than three self-swabs was defined as culture of S. aureus from all or all but one self-swabs.In all, 102 individuals underwent multi-site swabbing; S. aureus carriage was detected from at least one site from 40 individuals (39%). There was no difference between nose (29/102, 28%) and throat (28/102, 27%) isolation rates: the combination increased total detection rate by 10%. Ninety-nine patients returned any self-swab, and 96 returned more than three. Nasal carriage detection was not significantly different on nurse or self-swab [28/99 (74%) vs 26/99 (72%); ?2: P=0.75]. Twenty-two out of 25 participants with first self-swab positive were persistent carriers and 69/71 with first self-swab negative were not, giving high positive predictive value (88%), and very high negative predictive value (97%).Nasal swabs detected the majority of carriage; throat swabs increased detection by 10%. Self-taken nasal swabs were equivalent to nurse-taken swabs and predicted persistent nasal carriage over four weeks.