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Background <p>In Asian countries, <i>Klebsiella pneumoniae</i> is the predominant pathogen isolated from liver abscesses in patients with diabetes mellitus (DM). Elevated glucose level in DM patients causes various immune problems and may enhance <i>K. pneumoniae</i> virulence. Oxygen availability is another crucial factor influencing virulence factors expression during bacterial infections. The cyclic adenosine monophosphate (cAMP) receptor protein (CRP) plays a key role in mediating virulence factor expression in response to dynamic glucose levels in <i>K. pneumoniae</i>.</p> Results <p>This study investigated the regulation of CRP in type 3 fimbriae expression of <i>K. pneumoniae</i> CG43S3 in response to oxygen availability. We observed that anaerobically grown bacteria exhibited increased type 3 fimbriae expression. Glucose addition increased type 3 fimbriae expression under aerobic conditions but reduced it under anaerobic conditions. Exogenous cAMP supplementation complemented the biphasic role of glucose in response to oxygen availability. Deletion of <i>cyaA</i> (encoding adenylate cyclase) or <i>cpdA</i> (encoding phosphodiesterase) altered type 3 fimbriae expression, highlighting the role of cAMP signaling in this regulation. Under anaerobic conditions, CRP acted as an activator of type 3 fimbriae expression, contrasting with its repressive role under aerobic conditions. The biphasic regulatory activity of CRP was also observed in the promoter activity of cyclic diguanosine monophosphate (c-di-GMP)-related gene cluster <i>mrkHIJ</i> and the intracellular concentration of c-di-GMP. Among the nine c-di-GMP related genes containing a typical CRP binding site, the biphasic regulatory activity of CRP was also reflected in mediating the mRNA expression of D364_RS04770 (a putative diguanylate cyclase). Overexpression of D364_RS04770 not only increases type 3 fimbriae expression but also compensates for the absence of <i>crp</i>, further leading to the repression activity of CRP on type 3 fimbriae expression under anaerobic conditions. Furthermore, anaerobic conditions triggered the role of CRP in activating biofilm formation.</p> Conclusions <p>Our study identifies a novel oxygen-dependent switch in CRP function and highlights D364_RS04770 as a key downstream effector, distinguishing this mechanism from previously known glucose-dependent regulation in <i>K. pneumoniae</i> CG43S3. Additionally, D364_RS04770 may act as a mediator to influence the regulation of CRP on type 3 fimbriae expression in response to oxygen availability. Understanding these regulatory mechanisms provides a deeper insight into bacterial pathogenesis and potential therapeutic targets.</p>

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The dual role of cAMP receptor protein (CRP) in regulating type 3 fimbriae expression in Klebsiella pneumoniae CG43S3 in response to oxygen availability

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  • 发表日期：

    2026年6月1日

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  • Tien-Huang Lin,
  • Chen-Yu Wang,
  • Chien-Chen Wu,
  • Der-Yen Lee,
  • Ching-Ting Lin

摘要

Background

In Asian countries, Klebsiella pneumoniae is the predominant pathogen isolated from liver abscesses in patients with diabetes mellitus (DM). Elevated glucose level in DM patients causes various immune problems and may enhance K. pneumoniae virulence. Oxygen availability is another crucial factor influencing virulence factors expression during bacterial infections. The cyclic adenosine monophosphate (cAMP) receptor protein (CRP) plays a key role in mediating virulence factor expression in response to dynamic glucose levels in K. pneumoniae.

Results

This study investigated the regulation of CRP in type 3 fimbriae expression of K. pneumoniae CG43S3 in response to oxygen availability. We observed that anaerobically grown bacteria exhibited increased type 3 fimbriae expression. Glucose addition increased type 3 fimbriae expression under aerobic conditions but reduced it under anaerobic conditions. Exogenous cAMP supplementation complemented the biphasic role of glucose in response to oxygen availability. Deletion of cyaA (encoding adenylate cyclase) or cpdA (encoding phosphodiesterase) altered type 3 fimbriae expression, highlighting the role of cAMP signaling in this regulation. Under anaerobic conditions, CRP acted as an activator of type 3 fimbriae expression, contrasting with its repressive role under aerobic conditions. The biphasic regulatory activity of CRP was also observed in the promoter activity of cyclic diguanosine monophosphate (c-di-GMP)-related gene cluster mrkHIJ and the intracellular concentration of c-di-GMP. Among the nine c-di-GMP related genes containing a typical CRP binding site, the biphasic regulatory activity of CRP was also reflected in mediating the mRNA expression of D364_RS04770 (a putative diguanylate cyclase). Overexpression of D364_RS04770 not only increases type 3 fimbriae expression but also compensates for the absence of crp, further leading to the repression activity of CRP on type 3 fimbriae expression under anaerobic conditions. Furthermore, anaerobic conditions triggered the role of CRP in activating biofilm formation.

Conclusions

Our study identifies a novel oxygen-dependent switch in CRP function and highlights D364_RS04770 as a key downstream effector, distinguishing this mechanism from previously known glucose-dependent regulation in K. pneumoniae CG43S3. Additionally, D364_RS04770 may act as a mediator to influence the regulation of CRP on type 3 fimbriae expression in response to oxygen availability. Understanding these regulatory mechanisms provides a deeper insight into bacterial pathogenesis and potential therapeutic targets.