Richardson J D, Guo Emily, Wyllie Ryan M, Jensen Paul, Dawid Suzanne
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
mBio. 2025 Feb 5;16(2):e0299324. doi: 10.1128/mbio.02993-24. Epub 2024 Dec 17.
is an important human pathogen that normally resides in the human nasopharynx. Competence-mediated bacteriocin expression by plays a major role in both the establishment and persistence of colonization on this polymicrobial surface. Over 20 distinct bacteriocin loci have been identified in pneumococcal genomes, but only a small number have been characterized phenotypically. In this work, we demonstrate that three-fourths of strains contain a highly conserved locus that encodes an active lactococcin 972-like bacteriocin called streptococcin B. In these backgrounds, the locus is part of the early competence cascade due to a ComE binding site in the promoter region. Streptococcin B producing strains target both members of the population that have failed to activate competence and the 25% of the population that carry a naturally occurring deletion of the ComE binding site and the functional bacteriocin gene. The ComR-type regulator found directly upstream of the locus in strains can activate expression independent of the presence of the ComE binding site but only when stimulated by a peptide that is encoded in the locus of , a closely related bacterium that also inhabits the human nasopharynx. Given the co-regulation with competence and the phenotypic confirmation of activity, streptococcin B represents a previously unrecognized fratricide effector that gives producing strains an additional advantage over the naturally occurring deleted strains during colonization.
is a common cause of pneumonia, meningitis, sinusitis, and otitis media. In order to successfully colonize humans, a prerequisite to the development of invasive disease, must compete with other bacterial inhabitants of the nasal surface for space and nutrients. Bacteriocins are small antimicrobial peptides produced by bacteria that typically target neighboring bacteria by disruption of the cell surface. encodes a large number of potential bacteriocin, but, for most, their role in competitive interactions has not been defined. This work demonstrates that isolates that produce the bacteriocin streptococcin B have an advantage over non-producers. These observations contribute to our understanding of the competitive interactions that precede the development of disease.
是一种重要的人类病原体,通常存在于人类鼻咽部。通过能力介导的细菌素表达在这种多微生物表面的定殖建立和持续存在中起主要作用。在肺炎球菌基因组中已鉴定出20多个不同的细菌素基因座,但只有少数在表型上得到了表征。在这项工作中,我们证明四分之三的菌株含有一个高度保守的基因座,该基因座编码一种活性乳球菌素972样细菌素,称为链球菌素B。在这些背景下,由于启动子区域中的ComE结合位点,该基因座是早期能力级联反应的一部分。产生链球菌素B的菌株既靶向未能激活能力的群体成员,也靶向25%携带ComE结合位点和功能性细菌素基因自然缺失的群体。在肺炎链球菌菌株中,在该基因座直接上游发现的ComR型调节因子可以独立于ComE结合位点的存在激活表达,但仅在受到一种肽的刺激时才会激活,该肽由也栖息于人类鼻咽部的密切相关细菌口腔链球菌的该基因座编码。鉴于与能力的共同调节以及活性的表型确认,链球菌素B代表一种先前未被认识的自相残杀效应器,它使产生菌株在定殖过程中比自然发生的缺失菌株具有额外优势。
是肺炎、脑膜炎、鼻窦炎和中耳炎的常见病因。为了成功定殖于人类,这是侵袭性疾病发展的先决条件,肺炎链球菌必须与鼻腔表面的其他细菌居民竞争空间和营养。细菌素是细菌产生的小抗菌肽,通常通过破坏细胞表面来靶向邻近细菌。肺炎链球菌编码大量潜在的细菌素,但对于大多数细菌素而言,它们在竞争相互作用中的作用尚未明确。这项工作表明,产生细菌素链球菌素B的分离株比不产生的分离株具有优势。这些观察结果有助于我们理解肺炎链球菌疾病发展之前的竞争相互作用。