Biology subjects

Fisher, M. A.

Publications and source records attributed to Fisher, M. A..

4 recordsLinked to original sources

bioRxiv2024

Lineage-specific trait variation generates widespread, contemporaneous coexistence and competitive exclusion dynamics in an invasive, multihost wildlife parasite

Invasive and highly virulent parasites are emerging worldwide, transported to new locations and into novel hosts by anthropogenic activities. Multiple introduction events lead to interactions amongst genetically dissimilar genotypes that can result in either competitive exclusion, coexistence, or cycling through a combination of the two. Here, we report how intra-lineage trait variation of the multihost amphibian parasite Batrachochytrium dendrobatidis drives contrasting outcomes of inter-lineage interactions on two continents, Europe and Africa. Through field surveys, competition experiments and mathematical modelling we show that interactions between the same two lineages in the two continents and in different hosts demonstrate both ends of the exclusion/coexistence continuum. Trait variation in one of the two predominating lineages, BdGPL, is responsible for these contrasting outcomes: In Europe, BdGPL is highly competitive and has constrained the distribution of the other, BdCAPE, to two locations. In Africa, BdGPL and BdCAPE can mutually invade host populations when the other lineage is already resident, potentially leading to coinfections and recombination. That these contrasting outcomes are prolonged and contemporaneous for the same two lineages shows that epidemiological models of invasive parasites need to account for trait variation both within and across lineages.

ecology↗

bioRxiv2023

Antibacterial activity of Xenopsylla cheopis attacins against Yersinia pestis

Antimicrobial peptide resistance has been proposed to play a major role in the flea-borne transmission of Yersinia pestis. However, the antimicrobial peptide response in fleas and their interaction with Y. pestis is largely unknown. Attacins are one of the most abundantly expressed antimicrobial peptides within the first hours after Y. pestis infection of Xenopsylla cheopis, a major vector of plague. In this study, we report the cloning, expression, and purification of two X. cheopis attacin peptides and describe their interactions with and antimicrobial activities against Y. pestis. These flea attacins were shown to bind lipopolysaccharides and have potent activity against Y. pestis, however the mechanism of killing does not involve extensive membrane damage. Treatment with attacins rapidly inhibits Y. pestis colony formation and results in oxidative stress, yet live-cell imaging revealed that bacteria continue to grow and divide for several hours in the presence of attacins before undergoing morphological changes and subsequent lysis. This data provides insights into an early battle between vector and pathogen that may impact transmission of one of the most virulent diseases known to man.

microbiology↗

bioRxiv2023

Enterobacterial common antigen biosynthesis in Yersinia pestis is tied to antimicrobial peptide resistance

Resistance to antimicrobial peptides (AMPs) plays an important role in allowing Yersinia pestis to maintain a successful infection in the flea vector Xenopsylla cheopis. Mutants that are unable to modify lipid A in their outer membrane with aminoarabinose (Ara4N), showed increased sensitivity to AMPs such as polymyxin B (PB), as well as decreased survival in fleas. A deletion mutant of wecE, a gene involved in biosynthesis of enterobacterial common antigen (ECA), also displayed hypersusceptibility to PB in vitro. Additional mutants in the ECA biosynthetic pathway were generated, some designed to cause accumulation of intermediate products that sequester undecaprenyl phosphate (Und-P), a lipid carrier that is also used in numerous other pathways, including for peptidoglycan, O-antigen, and Ara4N biosynthesis. Mutants that accumulate Und-PP-linked intermediates (ECA-lipid II) showed increased susceptibility to PB, reduced Ara4N-modified lipid A, altered cell morphology, and decreased ability to maintain flea infections. These effects are consistent with a model where Y. pestis has a sufficiently limited free Und-P pool such that sequestration of Und-P as ECA-lipid II prevents adequate Ara4N biosynthesis, ultimately resulting in AMP hypersusceptibility.

microbiology↗

bioRxiv2021

Yersinia pestis lipopolysaccharide remodeling confers resistance to a Xenopsylla cheopis cecropin

Fleas are major vectors of Yersinia pestis, the causative agent of plague. It has been proposed that Y. pestis has developed the ability to overcome the innate immune responses of fleas. Despite the fact that they transmit a number of bacterial infections, very little is known about the immune responses in fleas. In this study, we describe the antimicrobial activities of cecropin from Xenopsylla cheopis (cheopin), a major vector for Y. pestis in the wild. This is the first cecropin-class antimicrobial peptide described from Siphonaptera insects. Cheopin showed potent activity against Gram-negative bacteria, but little activity against wild-type Y. pestis KIM6+. Deletion of the aminoarabinose operon, which is responsible for the 4-amino-4-deoxy-L-arabinose (Ara4N) modification of LPS, rendered Y. pestis highly susceptible to cheopin. Confocal microscopy and whole cell binding assays indicated that Ara4N modification reduces the affinity of cheopin for Y. pestis. Further, cheopin only permeabilized bacterial membranes in the absence of Ara4N-modified LPS, which was correlated with bacterial killing. This study provides insights into innate immunity of the flea and evidence for the crucial role of Ara4N modification of Y. pestis LPS in conferring resistance against flea antimicrobial peptides.

microbiology↗