The Agr-like quorum sensing system is required for pathogenesis of necrotic enteritis caused by Clostridium perfringens in poultry
Yu, Q., Lepp, D., Gohari, I.M., Wu, T., Zhou, H., Yin, X., Yu, H., Prescott, J.F., Nie, S.P., Xie, M.Y., Gong, J. (2017). The Agr-like quorum sensing system is required for pathogenesis of necrotic enteritis caused by Clostridium perfringens in poultry. Infection and Immunity, [online] 85(6), http://dx.doi.org/10.1128/IAI.00975-16
Plain language summary
Necrotic enteritis (NE) is a disease of broiler chickens that was estimated to cost the poultry industry $US 6 billion in production losses in 2015. NE is primarily controlled by in-feed antibiotics, a practice that is increasingly discouraged due to the risks of spreading antimicrobial resistance. It is therefore important to find alternative approaches to control NE, from both a financial and public health perspective. NE is caused by certain strains of Clostridium perfringens resulting from overgrowth of the bacterium in the intestine and production of toxins, particularly the NetB toxin. It has been shown that quorum-sensing (QS) systems, which are bacterial regulatory systems that allow bacterial pathogens to “sense” their population density, , can control their virulence. We therefore hypothesized that QS may play a role in the development of NE. To test this, we inactivated two key QS systems (LuxS and Agr-like) in a C. perfringens strain that causes NE, and measured both production of NetB toxin and ability to cause disease in a chicken model system. We found that the strain defective in the Agr-like QS system had drastically reduced production of NetB, and could no longer cause disease in chickens. These effects were reversed when the gene was reintroduced into the mutant. The identification of the Agr-like QS system as a key regulator of NE pathogenesis provides a new target to control NE. Future work will be focused on developing compounds that can interfere with this QS system and thereby protect against NE.
Clostridium perfringens encodes at least two different quorum sensing (QS) systems, the Agr-like and LuxS, and recent studies have highlighted their importance in the regulation of toxin production and virulence. The role of QS in the pathogenesis of necrotic enteritis (NE) in poultry and the regulation of NetB, the key toxin involved, has not yet been investigated. We have generated isogenic agrB-null and complemented strains from parent strain CP1 and demonstrated that the virulence of the agrB-null mutant was strongly attenuated in a chicken NE model system and restored by complementation. The production of NetB, a key NE-associated toxin, was dramatically reduced in the agrB mutant at both the transcriptional and protein levels, though not in a luxS mutant. Transwell assays confirmed that the Agrlike QS system controls NetB production through a diffusible signal. Global gene expression analysis of the agrB mutant identified additional genes modulated by Agrlike QS, including operons related to phospholipid metabolism and adherence, which may also play a role in NE pathogenesis. This study provides the first evidence that the Agr-like QS system is critical for NE pathogenesis and identifies a number of Agr-regulated genes, most notably netB, that are potentially involved in mediating its effects. The Agr-like QS system thus may serve as a target for developing novel interventions to prevent NE in chickens.