Divergent contributions of multiple PPIases to cell survival, sociality, and stress tolerance in Myxococcus xanthus DK1622

Abstract

ABSTRACT Peptidylprolyl isomerase (PPIase) catalyzes the rate-limiting step of proline cis-trans isomerization during protein folding. In bacteria, multiple PPIases are commonly present and participate in diverse physiological processes. Myxococcus xanthus DK1622 possesses as many as 17 PPIase genes. We previously reported the functional divergence of the four trigger factor family PPIases. Here, we systematically assessed the contributions of the remaining PPIases in cell survival, sociality, and stress tolerance. Pin1, localized in the periplasm, was essential for cell growth. Absence of the membrane-bound Pin3 impaired the social motility, predation ability, and sporulation but did not affect the fruiting body formation of M. xanthus. Furthermore, nearly all M. xanthus PPIases contributed to tolerance to environmental stresses. The transcriptional levels and expression patterns of these PPIases varied distinctly, even among members of the same family or with high sequence homology. Our findings provide a comprehensive view of functional divergences and suggest a potential functional cooperation network of PPIases in M. xanthus. IMPORTANCE Peptidylprolyl isomerase (PPIase), a ubiquitous enzyme present across nearly all kingdoms of life, catalyzes the cis-trans isomerization of peptidyl-prolyl bonds in polypeptide chains, thereby significantly accelerating protein folding. As a result, PPIases play critical roles in a wide range of physiological processes mediated by their substrate proteins. Myxobacteria are distinguished by their complex multicellular social behaviors. Among the 17 PPIases belonging to three families in Myxococcus xanthus DK1622, the membrane-bound Pin3, one of the SurA homologs, is involved in social behaviors such as social motility, predation, and sporulation. Given that PPIases are widely recognized as chaperones, our results also indicate that these M. xanthus PPIases extensively contribute to stress tolerance. Our findings underscore the essential functions of PPIases in cellular processes and reveal a correlation between the expansion of cellular functionalities and the functional evolution of PPIase proteins. Peptidylprolyl isomerase (PPIase), a ubiquitous enzyme present across nearly all kingdoms of life, catalyzes the cis-trans isomerization of peptidyl-prolyl bonds in polypeptide chains, thereby significantly accelerating protein folding. As a result, PPIases play critical roles in a wide range of physiological processes mediated by their substrate proteins. Myxobacteria are distinguished by their complex multicellular social behaviors. Among the 17 PPIases belonging to three families in Myxococcus xanthus DK1622, the membrane-bound Pin3, one of the SurA homologs, is involved in social behaviors such as social motility, predation, and sporulation. Given that PPIases are widely recognized as chaperones, our results also indicate that these M. xanthus PPIases extensively contribute to stress tolerance. Our findings underscore the essential functions of PPIases in cellular processes and reveal a correlation between the expansion of cellular functionalities and the functional evolution of PPIase proteins.