The role of cell-to-cell communication in Vibrio pathogenesis

Jung & Ng Spotlight

Wai-Leung Ng & Sarah Jung and the quorum sensing pathways they study

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Microbial group behaviors such as biofilm assembly, virulence factor production, and genetic exchange are important for bacteria to adapt to challenges encountered in their surrounding environment. However, without a collective effort, individual cells cannot carry out these processes effectively. Quorum-sensing (QS) is a cell-to-cell communication process that allows a group of bacteria to behave in unison. In this process, chemical signaling molecules (called autoinducers) are produced, secreted, and detected by every cell within a group in a cell density-dependent manner. At low cell density, when autoinducer concentration is low, there is little communication amongst individual bacterial cells. When bacteria grow and cell number increases, autoinducer concentration accumulates proportionally. Once autoinducer concentration reaches a detection threshold, all the cells respond to the signal and synchronously change their gene expression profile. Thus, through QS bacteria act collectively as a multi-cellular group

Vibrio cholerae, the causative agent for the diarrheal disease cholera, is a major public health concern in areas where water contamination is widespread, including parts of Asia, Africa, and Latin America. The WHO reports that there are several million reported cholera cases causing ~100,000 deaths every year, making the need for better prevention and treatment regimens imperative. Like many bacterial pathogens, V. cholerae depends on QS to regulate pathogenesis. Since its discovery, the V. cholerae QS system has served as a model to understand how pathogens employ QS for precise control of virulence factor production. Sarah Jung, a PhD student in the Molecular Microbiology graduate program, and her advisor Wai-Leung Ng focus on understanding the mechanisms underpinning QS in V. cholerae. They hope to develop new strategies to interfere communication in V. cholerae to control virulence in this devastating pathogen.

Two QS pathways have been previously established in V. cholerae. However, disruption of these two canonical pathways is insufficient to abolish V. cholerae communication. Importantly, these double sensory mutants are still virulent, suggesting additional communication means are adopted by V. cholerae to regulate virulence. The goal of Sarah’s thesis research is to identify these unknown QS pathways in V. cholerae. She discovered that two novel sensory inputs function in parallel with the two canonical pathways to regulate V. cholerae QS, and surprisingly any one of these communication pathways is enough to foster virulence. When these four pathways are disrupted together, the quadruple sensory mutants become avirulent. Why does V. cholerae perceive multiple parallel sensory inputs even if a single pathway appears to be capable to support effective communication? Sarah found that this specific QS network arrangement prevents untimely commitment to QS caused by external signal perturbations.

A premature switch to QS is unfavorable for V. cholerae pathogenesis since it adversely affects virulence factor production. Sarah’s research provides new insights into how bacterial pathogens integrate multiple sensory signals to elicit robust and coordinated QS responses. The uncovering of novel signaling pathways important for V. cholerae virulence could have significant ramifications for improving human health.

Jung SA, Chapman CA, Ng WL 2015. Quadruple quorum-sensing inputs control Vibrio cholerae virulence and maintain system robustness. PLoS Pathog. 11: e1004837. books

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