At least one hundred and fifty million people are diagnosed with urinary tract infections each year. While most infections are assumed to be caused by a single pathogen, multispecies urinary tract infections are more common than currently thought. The study “Multispecies bacterial invasion of human host cells” in Pathogens and Disease imaged different pathogens in bladder cells to better understand their interactions and thus the nature of infection, as discussed in this #FEMSmicroBlog by Charlotte Abell-King and Bill Söderström. #FascinatingMicrobes
The rise of multispecies superbug infections in urinary tracts
Due to the avalanche of antimicrobial-resistant bacteria, most patients diagnosed with bacterial infections will require multiple rounds of antibiotics. According to the WHO, superbugs cause ~5 million deaths yearly and are predicted to result in an additional $1 trillion in healthcare costs by 2025.
Hence, a lot of research focuses on understanding at a single-cell level how pathogens behave in infection settings and evade treatments. Using infection model systems, microfluidics and live cell fluorescence microscopy, several groups investigate the fundamentals of bacterial proliferation and division. By understanding how bacteria multiply in infection settings, we may learn to stop them from doing so.
From a clinical perspective, most urinary tract infections are diagnosed as single-species infections. Even when multiple bacterial species are detected, the most prominent bug is treated, and the others disregarded as sample contamination. Evidence suggests, however, that some pathogens associated with urinary tract infections are likely to live in multispecies communities.
Since little is known about the pathogenic mechanisms at the single bladder cell level, the study “Multispecies bacterial invasion of human host cells” in Pathogens and Disease observed interbacterial interactions in infection models.
After challenging human epithelial bladder cells, the study imaged them using high-resolution microscopy. The hypothesis was that distinct bacterial interactions within multispecies urinary tract infections would alter the nature of the infection.
Sharing is caring, even in the world of bacteria!
The work focussed on the infection strategies of the three pathogens: uropathogenic Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. Some combinations, for example, uropathogenic Escherichia coli and Enterococcus faecalis, led to elevated numbers of invaded bladder cells.
In comparison, other permutations, often including Klebsiella pneumoniae, did not. This was somewhat expected as in lab co-cultures, Klebsiella pneumoniae also inhibits the growth of other bacteria.
Uropathogenic Escherichia coli and Enterococcus faecalis were generally found in close proximity to one co-infected bladder cell. These two pathogens were considered to be highly ‘socially active’ since uropathogenic Escherichia coli often surrounded Enterococcus faecalis cells. This behaviour supports previous results and allows us to speculate that each species gains an advantage from the interaction, elevating invasion levels and, in the long run, prolonging infection.
When adding human urine to the infected cells, spectacular morphology changes happened in the Gram-negative uropathogenic Escherichia coli and Klebsiella pneumoniae. It is not fully clear yet why the bacteria change their shapes upon exposure to urine.
This adaptation could be part of a bacterial survival or colonisation mechanism since longer cells have the advantage of reaching bladder cells further away. In contrast, Gram-positive Enterococcus faecalis did not undergo infection-related filamentation.
The molecular mechanisms of this morphological change and, in general, the interbacterial interactions within the infection settings are yet to be fully characterised. Nevertheless, this study showed with visually stunning images, that pathogenic bacteria seem to collectively favour invading the same bladder cell.
The findings of this study only scratch the surface of the complex social interactions between different bacterial species in multispecies urinary tract infections. They represent a huge step forward to better understand one of the most common global infections.
- Read the article “Multispecies bacterial invasion of human host cells” by Abell-King et al. in Pathogens and Disease (2024).
About the authors of this blog
Charlotte Abell-King holds degrees from the University of Sydney and the University of Technology Sydney and is currently a PhD student at the Garvan Institute of Medical Research and the University of New South Wales. She is investigating the immune-metabolic axis of the mevalonate pathway in the lab of Prof. Mike Rogers. During her Honours year in the Söderström lab at UTS, Charlotte developed approaches to study bacterial multispecies invasion of human host cells in an UTI model system.
Bill Söderström is an ARC Future Fellow and the group leader of the Söderström lab at the Australian Institute for Microbiology and Infection at the University of Technology Sydney in Australia. Coming from an engineering physics background from KTH in Sweden, via a stint in the labs of Profs. Dan Daley and Gunnar von Heijne at Dept of Biochem & Biophys at Stockholm University and a bit cryo-EM at OIST in Japan, he is now running a research group mostly interested in imaging approaches to understand bacterial lifestyles in the test tube and in various infection models. Bill also welcomes students from Europe to join his lab in Sydney and to experience the Australian beach culture.
About this blog section
The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.
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