Biology subjects

Lehri, B.

Publications and source records attributed to Lehri, B..

4 recordsLinked to original sources

bioRxiv2024

Acanthamoeba castellanii as a model for unveiling Campylobacter jejuni host-pathogen dynamics

The persistence of the major enteric pathogen Campylobacter jejuni in the natural environment, despite being microaerophilic, remains unsolved. Its survival in the natural atmospheric environment likely stems from several factors, including interactions with amoebae. C. jejuni transiently interacts with Acanthamoebae and this is thought to provide protection against unfavourable atmospheric conditions and subsequently prime the bacteria for interactions with warm-blooded hosts. Acanthamoebae play vital roles in microbial ecosystems by preying on bacterial species, some of which are clinically important. We analysed the whole transcriptome of A. castellanii infected with C. jejuni 11168H. Our findings provide evidence that infection of A. castellanii with C. jejuni triggers distinct and reproducible cellular responses. Upregulated genes were associated with protein synthesis, DNA damage and repair, gluconeogenic pathways, and protein folding and targeting, while downregulated genes were involved in calcium ion transport, osmotic stress response, energy reserve metabolic processes, and protein hydroxylation. From this data we characterized Cj0979c, named here C. jejuni endonuclease (CjeN), which induces DNA damage in A. castellanii. High-resolution microscopy revealed an unexpected association between C. jejuni and host mitochondria, while infected cells show elevated cytosolic calcium levels and metabolic changes favouring "Warburg-like" metabolism. The increased lactate production was subsequently depleted, suggesting that this host metabolic by-product may support C. jejuni survival. These findings identify an unexpected interaction between amoebae and a microaerophilic bacterium and provides a useful model for further research on host-pathogen interactions.

microbiology↗

bioRxiv2023

Understanding Campylobacter coli isolates from the Vietnamese meat production network; a pilot study

Changing farming practices and the associated increase in the use of antibiotics are amongst the main drivers shaping the global increase of Campylobacter infections. The effects farming practices have on Campylobacter species, need to be studied at the global scale, particularly in emerging middle-income countries, where the demand for low-cost poultry meat is rising. While C. jejuni causes the majority of poultry associated diarrhoea, C. coli causes a significant amount of disease but are relatively understudied. In this study we characterised seven C. coli strains isolated from poultry farms and markets in Hanoi, Vietnam. Comprehensive data sets of bacterial Whole-Genome Sequencing; and phenotypic assays, such as, growth, motility, antimicrobial resistant testing along with virulence testing were performed to reveal the genetic relatedness and pathophysiological characteristics of seven C. coli strains. Six isolates were classified as multi-drug resistant, with all isolates resistant to ciprofloxacin, nalidixic acid and tetracycline, but susceptible to phenicols. All isolates had similar growth rates, while five were hyper-motile. Lethality of the isolates towards a tractable host-model system, larvae of the greater wax moth Galleria mellonella, often used to determine Campylobacter virulence was demonstrated for the first time for C. coli. Multilocus sequence typing data correlates with North American, European, and Asian isolates from patients suffering from gastroenteritis, emphasising the global spread of these strains. This work demonstrates that C. coli, with high levels of antimicrobial resistance, is an understudied global threat. Data summaryGenBank database with accession numbers JAKGTW000000000, JAKGTV000000000, JAKGTS000000000, JAKGTU000000000, JAKGTT000000000, JAKGTR000000000 and CP091310 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTW000000000 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTV000000000 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTS000000000 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTU000000000 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTT000000000 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTR000000000 https://www.ncbi.nlm.nih.gov/nuccore/CP091310.1 The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

microbiology↗

bioRxiv2022

Survival of Campylobacter jejuni in Acanthamoebae castellanii provides mechanistic insight into host pathogen interactions.

Campylobacter jejuni is the leading cause of bacterial foodborne gastroenteritis world-wide but is rarely transferred between human hosts. Although a recognized microaerophile, C. jejuni is incapable of growing in an aerobic environment. The persistence and transmission of this pathogen outside its warm-blooded avian and mammalian hosts is poorly understood. Acanthamoebae species, are predatory protists and form an important ecological niche with several bacterial species. Here, we investigate the interaction of C. jejuni and Acanthamoebae castellanii at the single-cell level. We observe that a subpopulation of C. jejuni cells can resist killing by A. castellanii and non-digested bacteria are released into the environment where they can persist. In addition, we observe that A. castellanii can harbor C. jejuni even upon encystment. Transcriptome analyses of C. jejuni interactions revealed similar survival mechanisms when infecting both A. castellanii and warm-blooded hosts. In particular, nitrosative stress defense mechanisms and flagellum function are important as confirmed by mutational analyses. This study describes a new host-pathogen interaction for C. jejuni and confirms that amoebae are transient hosts for the persistence, adaptability and potential transmission of C. jejuni.

microbiology↗

bioRxiv2021

Development of a novel glycoengineering platform for the rapid production of conjugate vaccines.

Antimicrobial resistance (AMR) is threatening the lives of millions worldwide. Antibiotics which once saved countless lives, are now failing, ushering in vaccines development as a current global imperative. Conjugate vaccines produced either by chemical synthesis or biologically in Escherichia coli cells, have been demonstrated to be safe and efficacious in protection against several deadly bacterial diseases. However, conjugate vaccines assembly and production have several shortcomings which hinders their wider availability. Here, we developed a tool, Mobile-element Assisted Glycoconjugation by Insertion on Chromosome, MAGIC, a novel method that overcomes the limitations of the current conjugate vaccine design method(s). We demonstrate at least 2-fold increase in glycoconjugate yield via MAGIC when compared to conventional bioconjugate method(s). Furthermore, the modularity of the MAGIC platform also allowed us to perform glycoengineering in genetically intractable bacterial species other than E. coli. The MAGIC system promises a rapid, robust and versatile method to develop vaccines against bacteria, especially AMR pathogens, and could be applied for biopreparedness.

microbiology↗