Targeting motility and chemotaxis as a strategy to combat bacterial pathogens

Matilla, Miguel A.; Krell, Tino

doi:10.1111/1751-7915.14306

Cited by 9 publications

(3 citation statements)

References 61 publications

(93 reference statements)

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“…As sensing of environmental signals is related to host colonization and the pathogenicity, the inhibition of bacterial sensory systems might constitute a promising alternative approach for the treatment of diseases ( Christensen et al, 2013 ; Taylor et al, 2022 ). Clinical studies have shown that omeprazole, an antibacterial medicine that disorients chemotactic bacteria, can increase the eradication rate of H. pylori from 25 to 95% upon combination with amoxicillin and clarithromycin ( Matilla and Krell, 2023 ; Zhou et al, 2023 ). Designing functional inhibitors that interfere with environmental sensing and signaling via signal transduction proteins may be a new strategy for disease prevention and control.…”

Section: Discussionmentioning

confidence: 99%

Identification of a dCache-type chemoreceptor in Campylobacter jejuni that specifically mediates chemotaxis towards methyl pyruvate

Zhao,

Yao,

et al. 2024

Front. Microbiol.

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The foodborne pathogenic bacterium Campylobacter jejuni utilizes chemotaxis to assist in the colonization of host niches. A key to revealing the relationship among chemotaxis and pathogenicity is the discovery of signaling molecules perceived by the chemoreceptors. The C. jejuni chemoreceptor Tlp11 is encoded by the highly infective C. jejuni strains. In the present study, we report that the dCache-type ligand-binding domain (LBD) of C. jejuni ATCC 33560 Tlp11 binds directly to novel ligands methyl pyruvate, toluene, and quinoline using the same pocket. Methyl pyruvate elicits a strong chemoattractant response, while toluene and quinoline function as the antagonists without triggering chemotaxis. The sensory LBD was used to control heterologous proteins by constructing chimeras, indicating that the signal induced by methyl pyruvate is transmitted across the membrane. In addition, bioinformatics and experiments revealed that the dCache domains with methyl pyruvate-binding sites and ability are widely distributed in the order Campylobacterales. This is the first report to identify the class of dCache chemoreceptors that bind to attractant methyl pyruvate and antagonists toluene and quinoline. Our research provides a foundation for understanding the chemotaxis and virulence of C. jejuni and lays a basis for the control of this foodborne pathogen.

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Section: Discussionmentioning

confidence: 99%

Identification of a dCache-type chemoreceptor in Campylobacter jejuni that specifically mediates chemotaxis towards methyl pyruvate

Zhao,

Yao,

et al. 2024

Front. Microbiol.

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“…However, a major bottleneck in microbiology is the fact that the signal that stimulates the large majority of receptors, including systems that have been extensively studied, is unknown (Krell, 2015 ). This information is not only required to understand the corresponding regulatory circuit but also desirable to develop novel antibacterial strategies that are based on interference with bacterial signal transduction (Matilla & Krell, 2023 ; Plotniece et al, 2023 ). One of the reasons for this lack of information is the fact that receptors can also be stimulated by the binding of signal‐loaded solute‐binding proteins (SBPs) instead of direct ligand binding (Matilla et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring solute binding proteins in Pseudomonas aeruginosa that bind to γ‐aminobutyrate and 5‐aminovalerate and their role in activating sensor kinases

Cerna‐Vargas,

Krell

2024

MicrobiologyOpen

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The standard method of receptor activation involves the binding of signals or signal‐loaded solute binding proteins (SBPs) to sensor domains. Many sensor histidine kinases (SHKs), which are activated by SBP binding, are encoded adjacent to their corresponding sbp gene. We examined three SBPs of Pseudomonas aeruginosa PAO1, encoded near the genes for the AgtS (PA0600) and AruS (PA4982) SHKs, to determine how common this arrangement is. Ligand screening and microcalorimetric studies revealed that the SBPs PA0602 and PA4985 preferentially bind to GABA (KD = 2.3 and 0.58 μM, respectively), followed by 5‐aminovalerate (KD = 30 and 1.6 μM, respectively) and ethanoldiamine (KD = 2.3 and 0.58 μM, respectively). In contrast, AgtB (PA0604) exclusively recognizes 5‐aminovaleric acid (KD = 2.9 μM). However, microcalorimetric titrations did not show any binding between the AgtS sensor domain and AgtB or PA0602, regardless of the presence of ligands. Similarly, bacterial two‐hybrid assays did not demonstrate an interaction between PA4985 and the AruS sensor domain. Therefore, sbp and shk genes located nearby are not always functionally linked. We previously identified PA0222 as a GABA‐specific SBP. The presence of three SBPs for GABA may be linked to GABA's role as a trigger for P. aeruginosa virulence.

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“…Mapping the chemosensing signals enteric bacteria perceive within the host can provide insight into pathogenesis and perhaps be a source of drug targets for inhibiting pathogen navigation and colonization 3,14 . Gut dysbiosis-a diseased host state induced by pathologies, inflammation and infections-exposes enteric bacteria to chemical stimuli distinct from that of a healthy gut that could encourage opportunistic pathogenesis 3,15 .…”

Section: Introductionmentioning

confidence: 99%

Bacterial vampirism mediated through taxis to serum

Glenn,

Gentry-Lear,

Shavlik

et al. 2023

Preprint

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Severe bacterial infections of the gastrointestinal (GI) tract instigate GI hemorrhaging that can lead to bacteremia, sepsis, and death. Pathogens preferentially colonize sites of injury, delaying healing and exacerbating tissue damage, but the underlying mechanisms are not well understood. We find that Enterobacteriaceae species are remarkably sensitive to human serum and perceive femtoliter quantities as a potent attractant. This behavior is driven by chemotaxis and the Tsr chemoreceptor, which recognizes L-serine present in serum. By studying the crystal structure of Salmonella Typhimurium Tsr, we identified a recognition motif for L-serine and found similar Tsr homologues in various Enterobacteriaceae species, including World Health Organization priority pathogens. Our analyses of Escherichia and Citrobacter bacteria, which also possess Tsr, confirm that these species exhibit chemoattraction to serum. We have coined the term 'vampirism' to describe this pathogenesis strategy and suggest it plays a role in injury tropism and increases the risk of bacteremia.

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Targeting motility and chemotaxis as a strategy to combat bacterial pathogens

Cited by 9 publications

References 61 publications

Identification of a dCache-type chemoreceptor in Campylobacter jejuni that specifically mediates chemotaxis towards methyl pyruvate

Identification of a dCache-type chemoreceptor in Campylobacter jejuni that specifically mediates chemotaxis towards methyl pyruvate

Exploring solute binding proteins in Pseudomonas aeruginosa that bind to γ‐aminobutyrate and 5‐aminovalerate and their role in activating sensor kinases

Bacterial vampirism mediated through taxis to serum

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