Polymicrobial interactions stimulate resistance to host innate immunity through metabolite perception

Abstract

Bacteria in the human oral cavity often grow in an attached multispecies biofilm community. Members of this community display defined interactions that have an impact on the physiology of the individual and the group. Here, we show that during coculture growth with streptococci, the oral pathogen Aggregatibacter actinomycetemcomitans displays enhanced resistance to killing by host innate immunity. The mechanism of resistance involves sensing of the streptococcal metabolite hydrogen peroxide by A. actinomycetemcomitans, which stimulates a genetic program resulting in enhanced expression of the complement resistance protein ApiA. The oxidative stress response regulator OxyR mediates induction of apiA transcription, and this induction is required for coculture resistance to killing by human serum. These findings provide evidence that interaction between community members mediates prokaryotic resistance to host innate immunity and reinforce the need to understand how polymicrobial growth affects interaction with the host immune system.Aggregatibacter ͉ ApiA ͉ complement ͉ peroxide ͉ Streptococcus gordonii

Peroxide‐Sensing Transcriptional Regulators in Bacteria

“…There is a growing realization of the role of peroxide-sensing regulators in adapting to this environmental shift through the control of processes such as virulence factor expression (74,90) and biofilm formation (99,119). Furthermore, the lethality of some antibiotics is due, at least in part, to increased production of ROS (58), and it has been demonstrated that the levels of oxidative stress protective enzymes can affect antibiotic resistance levels (6).…”

“…In the case of OxyR and PerR, their effect on virulence is not solely related to the regulation of oxidative stress defense genes. OxyR induces the expression of virulence factors that allow pathogens to evade host innate immunity (74,90), while PerR has been shown to directly regulate an extracellular virulence factor (mitogen factor 3) in Streptococcus pyogenes (117). Other clinically relevant processes, such as biofilm formation (99,119) and the oxidation state-independent regulation of several epigenetically controlled promoters determining phase variation (9,113,114), are also regulated by OxyR.…”

Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake

“…The expression of hofQ and that of the reference gene clpX (ATP-dependent Clp protease ATP-binding subunit ClpX) was determined by standard PCR (Phusion™ high-fidelity DNA polymerase, Thermo Fisher Scientific, F530L). ClpX was used as a control gene since this gene is known to be expressed in A. actinomycetemcomitans biofilm cultures [49]. PCR was performed using 100 ng of cDNA as a substrate.…”

Nitrite reductase is critical for Pseudomonas aeruginosa survival during co-infection with the oral commensal Streptococcus parasanguinis

“…Commensal and pathogenic bacteria frequently dwell within polymicrobial infections, and engage in interactions that impact both pathogenesis and the host response (Ramsey & Whiteley, 2009). Often, these consortia of bacteria work in concert to promote infection, cope with environmental stress, metabolize nutrients or resist clearing by the host immune response (Peters et al, 2012;Stacy et al, 2014).…”