Genome-Wide Analysis of Staphylococcus aureus Sequence Type 72 Isolates Provides Insights Into Resistance Against Antimicrobial Agents and Virulence Potential.

Nayab Batool,Akhilesh Kumar Chaurasia,Amen Shamim,Kyeong Kyu Kim

doi:10.3389/fmicb.2020.613800

Nayab Batool, Akhilesh Kumar Chaurasia + Show 2 more

Open Access

https://doi.org/10.3389/fmicb.2020.613800

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Abstract

Staphylococcus aureus sequence type 72 (ST72) is a major community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) that has rapidly entered the hospital setting in Korea, causing mild superficial skin wounds to severe bloodstream infections. In this study, we sequenced and analyzed the genomes of one methicillin-resistant human isolate and one methicillin-sensitive human isolate of ST72 from Korea, K07-204 and K07-561, respectively. We used a subtractive genomics approach to compare these two isolates to other 27 ST72 isolates to investigate antimicrobial resistance (AMR) and virulence potential. Furthermore, we validated genotypic differences by phenotypic characteristics analysis. Comparative and subtractive genomics analysis revealed that K07-204 contains methicillin (mecA), ampicillin (blaZ), erythromycin (ermC), aminoglycoside (aadD), and tetracycline (tet38, tetracycline efflux pump) resistance genes while K07-561 has ampicillin (blaZ) and tetracycline (tet38) resistance genes. In addition to antibiotics, K07-204 was reported to show resistance to lysostaphin treatment. K07-204 also has additional virulence genes (adsA, aur, hysA, icaABCDR, lip, lukD, sdrC, and sdrE) compared to K07-561, which may explain the differential virulence potential of these human isolates of ST72. Unexpectedly, the virulence potential of K07-561 was higher in an in vivo wax-worm infection model than that of K07-204, putatively due to the presence of a 20-fold higher staphyloxanthin concentration than K07-204. Comprehensive genomic analysis of these two human isolates, with 27 ST72 isolates, and S. aureus USA300 (ST8) suggested that acquisition of both virulence and antibiotics resistance genes by ST72 isolates might have facilitated their adaptation from a community to a hospital setting where the selective pressure imposed by antibiotics selects for more resistant and virulent isolates. Taken together, the results of the current study provide insight into the genotypic and phenotypic features of various ST72 clones across the globe, delivering more options for developing therapeutics and rapid molecular diagnostic tools to detect resistant bacteria.

Highlights

Staphylococcus aureus is a commensal organism of the skin and inhabitant of the nares in nearly 30% of the global human population (Krismer et al, 2017)
The rapid dissemination of CA-methicillin-resistant Staphylococcus aureus (MRSA) sequence type 72 (ST72) isolates into the hospital setting spurred scientists and clinicians to sequence the ST72 genome of Staphylococcus aureus CN1 (CP003979.1; Chen et al, 2013) to investigate the adaptability of ST72 isolates in the context of HA ST72-MRSA infections
CP012119) revealed the presence and distribution of 10 additional antibiotics genes, namely blaZ, aadD, ermC, tetK, mphC, msr(A), aph(3')-III, aac(6')-aph(2'), fusC, and dfrG genes conferring the resistance against their corresponding antibiotics (Figure 1A)

Summary

INTRODUCTION

Staphylococcus aureus is a commensal organism of the skin and inhabitant of the nares in nearly 30% of the global human population (Krismer et al, 2017). It is important to further our understanding of the genotypic and phenotypic features of various ST72 clones across the globe to assess current and future therapeutic options, to facilitate rapid molecular diagnosis, and to allow effective measures to be devised to reduce their rapid dissemination. No genome-wide comprehensive analyses of the genotypic and phenotypic correlations between antibiotic resistance and acquisition of isolate-specific virulence genes has been performed. The rapid dissemination of CA-MRSA ST72 isolates into the hospital setting spurred scientists and clinicians to sequence the ST72 genome of Staphylococcus aureus CN1 (CP003979.1; Chen et al, 2013) to investigate the adaptability of ST72 isolates in the context of HA ST72-MRSA infections. The genome-wide analyses provided the isolatespecific antibiotics resistance and virulence genes among various ST72 isolates which could be useful in determining the current and future therapeutic options and facilitate rapid molecular diagnosis of ST72 isolates

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RESULTS AND DISCUSSION

DATA AVAILABILITY STATEMENT

CONCLUSIONS