Insights from protein-protein interaction studies on bacterial pathogenesis

ABSTRACT

Introduction: The threat bacterial pathogens pose to human health is increasing with the number and distribution of antibiotic-resistant bacteria, while the rate of discovery of new antimicrobials dwindles. Proteomics is playing key roles in understanding the molecular mechanisms of bacterial pathogenesis, and in identifying disease outcome determinants. The physical associations identified by proteomics can provide the means to develop pathogen-specific treatment methods that reduce the spread of antibiotic resistance and alleviate the negative effects of broad-spectrum antibiotics on beneficial bacteria.

Areas covered: This review discusses recent trends in proteomics and introduces new and developing approaches that can be applied to the study of protein-protein interactions (PPIs) underlying bacterial pathogenesis. The approaches examined encompass options for mapping proteomes as well as stable and transient interactions in vivo and in vitro. We also explored the coverage of bacterial and human-bacterial PPIs, knowledge gaps in this area, and how they can be filled.

Expert commentary: Identifying potential antimicrobial candidates is confounded by the complex molecular biology of bacterial pathogenesis and the lack of knowledge about PPIs underlying this process. Proteomics approaches can offer new perspectives for mechanistic insights and identify essential targets for guiding the discovery of next generation antimicrobials.

KEYWORDS:

• Bacterial pathogen-host interactions
• bacterial pathogenesis
• mass spectrometry
• proteomics
• protein-protein interactions
• protein complementation assays
• Salmonella enterica serovar Typhimurium
• systems biology

Acknowledgments

We thank Drs. M. Jessulat and J. Vlasblom (Babu laboratory) and Dr. G. Musso (Harvard Medical School) for providing comments during the preparation of this manuscript.

Disclosure of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Supplemental Material

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Additional information

Funding

This paper was supported by the Saskatchewan Health Research Foundation and Canadian Institutes of Health Research (CIHR) Postdoctoral Fellowship (AG), and the Natural Sciences and Engineering Research Council of Canada: DG-20234 and CIHR: PJT −148831(MB).