Listeria monocytogenes Has Both Cytochrome bd -Type and Cytochrome aa ₃ -Type Terminal Oxidases, Which Allow Growth at Different Oxygen Levels, and Both Are Important in Infection

Abstract

Listeria monocytogenes is a foodborne pathogen responsible for a number of life-threatening infections of humans. During an infection, it invades epithelial cells before spreading from the intestine to the cells of the liver and spleen. This requires an ability to adapt to varying oxygen levels. Here, we demonstrate that L. monocytogenes has two terminal oxidases, a cytochrome bd-type (CydAB) and a cytochrome aa3-type menaquinol (QoxAB) oxidase, and that both are used for respiration under different oxygen tensions. Furthermore, we show that possession of both terminal oxidases is important in infection. In air, the CydAB bd-type oxidase is essential for aerobic respiration and intracellular replication, and cydAB mutants are highly attenuated in mice. In contrast, the QoxAB aa3-type oxidase is required neither for aerobic respiration in air nor for intracellular growth. However, the qoxAB mutants are attenuated in mice, with a delay in the onset of disease signs and with increased survival time, indicating a role for the QoxAB aa3-type oxidase in the initial stages of infection. Growth of bacteria under defined oxygen conditions revealed that at 1% (vol/vol), both oxidases are functional, and the presence of either is sufficient for aerobic respiration and intracellular replication. However, at 0.2% (vol/vol), both oxidases are necessary for maximum growth. These findings are consistent with the ability of L. monocytogenes to switch between terminal oxidases under different oxygen conditions, providing exquisite adaptation to different conditions encountered within the infected host.

Initial Transcriptomic Response and Adaption of Listeria monocytogenes to Desiccation on Food Grade Stainless Steel

“…The last gene in the salt shock induced operon, pdhD, was upregulated at all times, however, this was not significant (p > 0.05) after desiccation for 6 and 24 h in Lm 568 and Lm 08-5578, respectively. The σ B -regulated quinol oxidase operon (qoxABCD), which encodes cytochrome aa 3 and is involved in oxidative stress response and required for aerobic growth (Corbett et al, 2017;Liu et al, 2017a), was part of the shared core response to desiccation with upregulation of all four genes ( Table 2). The importance of oxidative stress is supported by the observed upregulation of ctaB, which is needed for biosynthesis of the prosthetic group in cytochrome aa 3 (Svensson et al, 1993).…”

Host immunity increasesMycobacterium tuberculosisreliance on cytochromebdoxidase

“…The flexibility of bacterial respiratory chains facilitates adaptation to changing environments, and in many situations the bd oxidase becomes critical under conditions where the bc 1 /aa 3 complex is inhibited. In pathogens such as E.coli, Listeria monocytogenes, and Salmonella typhimuirium, the requirement for the cytochrome bd oxidase in bacterial virulence has been attributed to its role in resisting hypoxia and nitrosative and oxidative stress (23)(24)(25)(26). While previous studies in M. marinum and M. smegmatis found that the mycobacterial bd oxidase can also confer resistance to hypoxia and peroxide, the specific roles played by the cytochrome bd and bc 1 /aa 3 oxidases of Mtb during infection has been less clear.…”

Deletion of glutaredoxin promotes oxidative tolerance and intracellular infection in Listeria monocytogenes

“…Relevant to pathophysiology, cytochrome oxidases are expressed in a number of bacterial pathogens. These include Salmonella [35], Mycobacterium tuberculosis [36], Shigella flexneri [37], Streptococcus [38], and L. monocytogenes [39,40]. The cytochrome oxidases have been studied to play a role of in bacterial protection against oxidative stress.…”