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The COVID-19 pandemic has the potential to affect the human microbiome in infected and uninfected individuals, having a substantial impact on human health over the long term. This pandemic intersects with a decades-long decline in microbial diversity and ancestral microbes due to hygiene, antibiotics, and urban living (the hygiene hypothesis). High-risk groups succumbing to COVID-19 include those with preexisting conditions, such as diabetes and obesity, which are also associated with microbiome abnormalities. Current pandemic control measures and practices will have broad, uneven, and potentially long-term effects for the human microbiome across the planet, given the implementation of physical separation, extensive hygiene, travel barriers, and other measures that influence overall microbial loss and inability for reinoculation. Although much remains uncertain or unknown about the virus and its consequences, implementing pandemic control practices could significantly affect the microbiome. In this Perspective, we explore many facets of COVID-19−induced societal changes and their possible effects on the microbiome, and discuss current and future challenges regarding the interplay between this pandemic and the microbiome. Recent recognition of the microbiome’s influence on human health makes it critical to consider both how the microbiome, shaped by biosocial processes, affects susceptibility to the coronavirus and, conversely, how COVID-19 disease and prevention measures may affect the microbiome. This knowledge may prove key in prevention and treatment, and long-term biological and social outcomes of this pandemic.

Autoinducer 2 (AI-2) is widely recognized as a signal molecule for intra-and interspecies communication inGram-negative bacteria, but its signaling function in Gram-positive bacteria, especially in Staphylococcus aureus, remains obscure. Here we reveal the role of LuxS in the regulation of capsular polysaccharide synthesis in S. aureus NCTC8325 and show that AI-2 can regulate gene expression and is involved in some physiological activities in S. aureus as a signaling molecule. Inactivation of luxS in S. aureus NCTC8325 resulted in higher levels of transcription of capsular polysaccharide synthesis genes. The survival rate of the luxS mutant was higher than that of the wild type in both human blood and U937 macrophages. In comparison to the luxS mutant, a culture supplemented with chemically synthesized 4,5-dihydroxy-2,3-pentanedione (DPD), the AI-2 precursor molecule, restored all the parental phenotypes, suggesting that AI-2 has a signaling function in S. aureus. Furthermore, we demonstrated that the LuxS/AI-2 signaling system regulates capsular polysaccharide production via a two-component system, KdpDE, whose function has not yet been clarified in S. aureus. This regulation occurred via the phosphorylation of KdpE binding to the cap promoter.Quorum sensing (QS) is a cell-cell communication mechanism in which bacteria secrete and sense small diffusible molecules called autoinducers (AIs) to coordinate social activities, such as bioluminescence, biofilm formation, swarming behavior, antibiotic production, and virulence factor secretion (7,23,38,59). Many QS mechanisms have evolved among bacteria. In general, Gram-negative bacteria use acylated homoserine lactones (AHLs) as AIs, and Gram-positive bacteria use oligopeptide AIs, which act through two-component phosphorelay cascades. Studies have shown that one QS mechanism is shared by both Gram-positive and Gram-negative bacteria and involves the production of autoinducer 2 (AI-2) (4, 38, 59, 60), which is synthesized by the LuxS enzyme in a metabolic pathway known as the activated methyl cycle (50,57,61). AI-2 is not a single compound but a family of interconverting compounds derived from 4,5-dihydroxy-2,3-pentanedione (DPD), which cyclizes spontaneously to form two epimeric furanoses, (2R,4S)-and (2S,4S)-2,4-dihydroxy-2-methyldihydrofuran-3-one (R-and S-DHMF), respectively. Hydration of R-and S-DHMF produces (2R, 4S)-and (2S, 4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran (R-and S-THMF), respectively (40). In contrast to the other autoinducers that are usually involved in intraspecies communication, AI-2 is widely present in bacteria, leading to the suggestion that it is a universal language for interspecies communication (50,64).The LuxS/AI-2 system is a more recently described QS system which was first identified in Vibrio harveyi, where it functions as part of a complex multilayered QS system to regulate bioluminescence (9, 10). LuxS plays a metabolic role in the activated methyl cycle, and one molecule of DPD is formed as a by-product every one cycle. Thi...