Hardy Britney L, Bansal Garima, Hewlett Katharine H, Arora Arshia, Schaffer Scott D, Kamau Edwin, Bennett Jason W, Merrell D Scott
Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Department of Clinical Microbiology, Walter Reed National Military Medical Center, Bethesda, MD, United States.
Front Microbiol. 2020 Jan 15;10:2977. doi: 10.3389/fmicb.2019.02977. eCollection 2019.
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 . Despite this, exists as part of the microbiota of ∼25% of the population, suggesting that the interplay between and commensals can be complex. Microbiota studies indicate that several bacterial genera are negatively correlated with 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 activity, we screened a small collection of clinical isolates from the Walter Reed National Military Medical Center for the ability to inhibit multiple strains. We found that the majority of the isolates (82%) inhibited at least one strain; 23% inhibited all strains tested. In total, seven isolates mediated inhibitory activity that was independent of physical contact with , and seven isolates mediated bactericidal activity. 16S rRNA based-sequencing revealed that the inhibitory isolates belonged to the , , , , , and genera. Unexpectedly, these included seven distinct isolates, all of which showed heterogeneous degrees of anti- 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 significantly decreased mortality of -infected 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 and other pathogens.
细菌通常存在于多种微生物群落中，它们会争夺有限的资源。这种竞争的内在因素是某些物种抑制或杀死其竞争者的能力。这种现象在人体中普遍存在，共生细菌会阻止外来微生物的定植。在这方面，分子流行病学和基于微生物群的研究表明，物种特异性相互作用在预防机会性病原体的鼻腔定植中起着关键作用。尽管如此，[某种细菌]在约25%的人群微生物群中存在，这表明[该细菌]与共生菌之间的相互作用可能很复杂。微生物群研究表明，几个细菌属与[该细菌]的定植呈负相关。虽然这些研究概述了细菌的存在情况，但它们往往无法确定个体物种特异性相互作用；对这一领域有更深入的了解可能有助于开发新型抗菌药物。作为一项旨在鉴定具有抗[该细菌]活性的单个细菌物种的概念验证研究，我们筛选了一小批来自沃尔特里德国家军事医疗中心的临床分离株，以检测它们抑制多种[该细菌]菌株的能力。我们发现，大多数分离株（82%）至少抑制一种[该细菌]菌株；23%抑制了所有测试的[该细菌]菌株。总共有七种分离株介导了与[该细菌]无物理接触的抑制活性，七种分离株介导了杀菌活性。基于16S rRNA的测序显示，具有抑制作用的分离株属于[具体细菌属名称1]、[具体细菌属名称2]、[具体细菌属名称3]、[具体细菌属名称4]、[具体细菌属名称5]和[具体细菌属名称6]属。出乎意料的是，其中包括七种不同的[该细菌]分离株，所有这些分离株都表现出不同程度的抗[该细菌]活性。对特定分离株进行的明确机制研究表明，抑制活性保留在源自这些分离株的条件性无细胞培养基（CCFM）中。此外，从[具体细菌属名称]获得的CCFM显著降低了感染[该细菌]的[某种昆虫]幼虫的死亡率。虽然未来的研究将试图确定抑制活性的分子机制，但我们目前的研究结果支持将多种微生物相互作用的研究作为一种策略，以了解细菌竞争并鉴定针对[该细菌]和其他病原体的新型疗法。
