Abstract

Bacteria evolved multiple strategies to survive and develop optimal fitness in their ecological niche. They deployed protein secretion systems for robust and efficient delivery of antibacterial toxins into their target cells, therefore inhibiting their growth or killing them. To maximize antagonism, recipient factors on target cells can be recognized or hijacked to enhance the entry or toxicity of these toxins. To date, knowledge regarding recipient susceptibility (RS) factors and their mode of action is mostly originating from studies on the type Vb secretion system that is also known as the contact-dependent inhibition (CDI) system. Yet, recent studies on the type VI secretion system (T6SS), and the CDI by glycine-zipper protein (Cdz) system, also reported the emerging roles of RS factors in interbacterial competition. Here, we review these RS factors and their mechanistic impact in increasing susceptibility of recipient cells in response to CDI, T6SS, and Cdz. Past and future strategies for identifying novel RS factors are also discussed, which will help in understanding the interplay between attacker and prey upon secretion system-dependent competition. Understanding these mechanisms would also provide insights for developing novel antibacterial strategies to antagonize aggressive bacteria-killing pathogens.

Highlights

  • Bacteria are one of the most abundant forms of life on earth, and they have developed multiple strategies to compete with each other and fight for limited resources and space (Foster and Bell, 2012; Ghoul and Mitri, 2016)

  • The confirmed recipient susceptibility (RS)-encoding genes include clpA, clpP, gltA, ydhS, ydaE, and cbpA, all encoding cytosolic proteins. These results suggest that the RS factors affecting A. tumefaciens T6SS killing outcome are rather involved after injection of T6SS toxins into the recipient cells

  • Accumulating evidence indicated that T6SSs in commensal bacteria such as Bacteroides fragilis and Pseudomonas protegens play a critical role in the defense against invading bacterial pathogens and impact microbial community in the gut of mammalian and insect, respectively (Chatzidaki-Livanis et al, 2016; Wexler et al, 2016; Vacheron et al, 2019)

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Summary

INTRODUCTION

Bacteria are one of the most abundant forms of life on earth, and they have developed multiple strategies to compete with each other and fight for limited resources and space (Foster and Bell, 2012; Ghoul and Mitri, 2016). Basal levels of T6SS transcripts were detected when confronted with harmless recipient cells, while upregulation occurs at moderate or higher levels when confronted with contender or aggressive competitors (Lazzaro et al, 2017) Overall, these findings unveil the importance of kin recognition in determining the outcome of the T6SS attack, but future systematic analysis is required to identify bond formation for activity of incoming periplasmic toxins in the genetic features or determinants governing the fate of a the recipient cell is likely a widespread mechanism (Figure 5; competition (Figure 5). The confirmed RS-encoding genes include clpA, clpP, gltA, ydhS, ydaE, and cbpA, all encoding cytosolic proteins These results suggest that the RS factors affecting A. tumefaciens T6SS killing outcome are rather involved after injection of T6SS toxins into the recipient cells. With the availability of the E. coli Keio library containing 3,909 knockout mutant strains (Baba et al, 2006), an HTS with the aid of TABLE 2 | Summary of current and potential methods for discovery of recipient susceptibility (RS) factors

Approach Method
Co-purification
DISCUSSION
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