AUTHOR=Hardy Britney L. , Bansal Garima , Hewlett Katharine H. , Arora Arshia , Schaffer Scott D. , Kamau Edwin , Bennett Jason W. , Merrell D. Scott 

TITLE=Antimicrobial Activity of Clinically Isolated Bacterial Species Against Staphylococcus aureus

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02977

DOI=10.3389/fmicb.2019.02977

ISSN=1664-302X

ABSTRACT=<p>Bacteria often exist in polymicrobial communities where they compete for limited resources. Intrinsic to this competition is the ability of some species to inhibit or kill their competitors. This phenomenon is pervasive throughout the human body where commensal bacteria block the colonization of incoming microorganisms. In this regard, molecular epidemiological and microbiota-based studies suggest that species-specific interactions play a critical role in the prevention of nasal colonization of the opportunistic pathogen <italic>Staphylococcus aureus</italic>. Despite this, <italic>S. aureus</italic> exists as part of the microbiota of ∼25% of the population, suggesting that the interplay between <italic>S. aureus</italic> and commensals can be complex. Microbiota studies indicate that several bacterial genera are negatively correlated with <italic>S. aureus</italic> colonization. While these studies paint a broad overview of bacterial presence, they often fail to identify individual species-specific interactions; a greater insight in this area could aid the development of novel antimicrobials. As a proof of concept study designed to identify individual bacterial species that possess anti<italic>-S. aureus</italic> activity, we screened a small collection of clinical isolates from the Walter Reed National Military Medical Center for the ability to inhibit multiple <italic>S. aureus</italic> strains. We found that the majority of the isolates (82%) inhibited at least one <italic>S. aureus</italic> strain; 23% inhibited all <italic>S. aureus</italic> strains tested. In total, seven isolates mediated inhibitory activity that was independent of physical contact with <italic>S. aureus</italic>, and seven isolates mediated bactericidal activity. 16S rRNA based-sequencing revealed that the inhibitory isolates belonged to the <italic>Acinetobacter</italic>, <italic>Agromyces</italic>, <italic>Corynebacterium</italic>, <italic>Microbacteria</italic>, <italic>Mycobacterium</italic>, and <italic>Staphylococcus</italic> genera. Unexpectedly, these included seven distinct <italic>Acinetobacter baumannii</italic> isolates, all of which showed heterogeneous degrees of anti-<italic>S. aureus</italic> activity. Defined mechanistic studies on specific isolates revealed that the inhibitory activity was retained in conditioned cell free medium (CCFM) derived from the isolates. Furthermore, CCFM obtained from <italic>S. saprophyticus</italic> significantly decreased mortality of <italic>S. aureus</italic>-infected <italic>Galleria mellonella</italic> caterpillars. While future studies will seek to define the molecular mechanisms of the inhibitory activities, our current findings support the study of polymicrobial interactions as a strategy to understand bacterial competition and to identify novel therapeutics against <italic>S. aureus</italic> and other pathogens.</p>