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. 2013 May 16:13:221.
doi: 10.1186/1471-2334-13-221.

Longitudinal genetic analyses of Staphylococcus aureus nasal carriage dynamics in a diverse population

Gowrishankar Muthukrishnan  1 , Ryan P Lamers, Austin Ellis, Vanathy Paramanandam, Alana B Persaud, Sergio Tafur, Christopher L Parkinson, Alexander M Cole
Affiliations

Longitudinal genetic analyses of Staphylococcus aureus nasal carriage dynamics in a diverse population

Gowrishankar Muthukrishnan et al. BMC Infect Dis. .

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

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Figures

Figure 1
Figure 1
Distribution of SA nasal carrier indices among 109 healthy individuals monitored longitudinally. Carrier index is defined as the number of SA positive nasal swabs over number of total swabs for each individual person. A total of 61 SA nasal carriers and 48 non-carriers were monitored longitudinally and their respective carrier indices are represented here. NC, indicates SA non-carrier state; SA intermittent carriage state; and PC, SA persistent carriage state.
Figure 2
Figure 2
SA strains from persistent and intermittent nasal carriers are genetically related to nosocomial epidemic strains. (A) Bayesian MCMC analysis of persistent carrier strains (colored in blue), intermittent carrier strains (colored in black) and nosocomial epidemic strains (colored in red). Numbers at each node indicate posterior probability support and grey-filled circles represent 100% posterior probability. (B) eBURST analysis of the MLST data clusters STs from intermittent and persistent carriers into same clonal complexes and into groups that are represented by numbers in grey. STs colored in black are nasal carrier strains, STs colored in red are epidemic strains and those in green contain both carrier and epidemic strains. Circle sizes in each cluster are proportional to the number of isolates and blue circles are founders of that particular cluster.
Figure 3
Figure 3
Longitudinal monitoring reveals that SA strains from both persistent and intermittent nasal carriers change over time. A representative set of persistent and intermittent carriers that have been monitored for at least one year is depicted here. (C) indicates SA nasal carriage at the time of swabbing and (N) indicates SA non-carrier state. Colors represented in the figure correspond to different Sequence Types (STs) identified by MLST. STs are segregated into different cluster groups by eBURST analysis. Carriers within the same household are grouped next to each other (indicated by * and flower bracket). (NA) corresponds to ST not available.
Figure 4
Figure 4
Genotyping of hypervariable virulence genes revealed no preferential colonization of specific genotypes of SA strains in persistent and intermittent carriers. (A) eBURP clustering analysis based on spa types revealed that both persistent and intermittent carrier strains belonged to same clonal complexes. spa types colored in blue contain only persistent carriers while those in black contain only intermittent carriers. spa types colored in green contain both intermittent and persistent carriers. Circle sizes in each cluster are proportional to the number of isolates and inferred founders (blue circles) and sub-founders (yellow circles) of each cluster are also represented here. spa types with less than 5 repeats were excluded from the eBURP analysis. (B) A representative set of SA persistent (colored in blue) and intermittent (colored in black) carrier strains having indistinguishable clfB R domain repeat region sequences. Like-colored boxes indicate 100% sequence similarity between SA strains.
Figure 5
Figure 5
spa and clfB repeat domain lengths are indistinguishable between persistent and intermittent carriers. Plots comparing X domain repeat region of spa and R region lengths of clfB between persistent and intermittent carrier SA strains.
See this image and copyright information in PMC

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