Acid resistance system CadBA is implicated in acid tolerance and biofilm formation and is identified as a new virulence factor of Edwardsiella tarda

Abstract

Edwardsiella tarda is a facultative intracellular pathogen in humans and animals. The Gram-negative bacterium is widely considered a potentially important bacterial pathogen. Adaptation to acid stress is important for the transmission of intestinal microbes, so the acid-resistance (AR) system is essential. However, the AR systems of E. tarda are totally unknown. In this study, a lysine-dependent acid resistance (LDAR) system in E. tarda, CadBA, was characterized and identified. CadB is a membrane protein and shares high homology with the lysine/cadaverine antiporter. CadA contains a PLP-binding core domain and a pyridoxal phosphate-binding motif. It shares high homology with lysine decarboxylase. cadB and cadA are co-transcribed under one operon. To study the function of the cadBA operon, isogenic cadA, cadB and cadBA deletion mutant strains TX01ΔcadA, TX01ΔcadB and TX01ΔcadBA were constructed. When cultured under normal conditions, the wild type strain and three mutants exhibited the same growth performance. However, when cultured under acid conditions, the growth of three mutants, especially TX01ΔcadA, were obviously retarded, compared to the wild strain TX01, which indicates the important involvement of the cadBA operon in acid resistance. The deletion of cadB or cadA, especially cadBA, significantly attenuated bacterial activity of lysine decarboxylase, suggesting the vital participation of cadBA operon in lysine metabolism, which is closely related to acid resistance. The mutations of cadBA operon enhanced bacterial biofilm formation, especially under acid conditions. The deletions of the cadBA operon reduced bacterial adhesion and invasion to Hela cells. Consistently, the deficiency of cadBA operon abated bacterial survival and replication in macrophages, and decreased bacterial dissemination in fish tissues. Our results also show that the expression of cadBA operon and regulator cadC were up-regulated upon acid stress, and CadC rigorously regulated the expression of cadBA operon, especially under acid conditions. These findings demonstrate that the AR CadBA system was a requisite for the resistance of E. tarda against acid stress, and played a critical role in bacterial infection of host cells and in host tissues. This is the first study about the acid resistance system of E. tarda and provides new insights into the acid-resistance mechanism and pathogenesis of E. tarda.

Resistance Patterns of Frequently Applied Antimicrobials and Occurrence of Antibiotic Resistance Genes in Edwardsiella tarda Detected in Edwardsiellosis-Infected Tilapia Species of Fish Farms of Punjab in Pakistan

“…Edwardsiellosis outbreaks have caused significant losses at farms of various fish species in aquaculture [17]. Its causative agent, Edwardsiella tarda, is a gram-negative bacterium, a facultatively intracellular pathogen, and one of the emerging top causative pathogens [18,19] of systemic hemorrhagic septicemic infection in fish, namely edwardsiellosis and hemorrhagic septicemia [16,20,21]. E. tarda has caused mass mortality in a wide variety of wild and cultured fish species of both marine and freshwater environments worldwide [22], especially in Oreochromis niloticus, Cyprinus carpio, Labeo rohita, Clarias gariepinus, Seriola quinqueradiata, Anguilla japonica, and Pagrus major [20,23,24].…”

The Immunoprotection of OmpH Gene Deletion Mutation of Pasteurella multocida on Hemorrhagic Sepsis in Qinghai Yak

“…DNA J is among the most important members of the HSP family. It is a molecular chaperone that stimulates ATPase and folding of HSP70 DNA K. DNA J is a virulence factor critical to the pathogenesis of bacteria such as Edwardsiella tarda [ 33 ]. Mucosal immunization with DNA J induces mucosal immunity and stimulates the secretion of IL-10 and IFN-γ and IL-17A, which reduces colonization of pneumococcal bacteria in the nose and lung.…”

Recent insights into the world of dual‐function bacterial sRNAs

“…The system is induced under anaerobic and acidic growth conditions and provides resistance to weak organic acids produced during carbohydrate fermentation under oxygen and phosphate deficiency (Kanjee & Houry, 2013;Zhao & Houry, 2010), resulting in reduced biofilm formation. (Du et al, 2021). AzuCR binds near the ribosome binding site of cadA mRNA, thus likely blocking ribosome binding (Raina et al, 2022).…”