Survival of Campylobacter jejuni 11168H in Acanthamoebae castellanii Provides Mechanistic Insight into Host Pathogen Interactions

Nasher, Fauzy; Lehri, Burhan; Horney, Megan F.; Stabler, Richard A.; Wren, Brendan W.

doi:10.3390/microorganisms10101894

Cited by 5 publications

(18 citation statements)

References 75 publications

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“… C. jejuni 11168H flagella mutants abolished uptake by A. castellanii [11]. Here, live-cell imaging revealed that the C.…”

Section: Resultsmentioning

confidence: 99%

“… C. jejuni aggregate on the surface of Acanthamoebae prior to phagocytosis [10, 11], although it is now apparent that this aggregation is not essential to induce a productive internalization given that phagocytosis of the ∆ flaB mutant was dramatically reduced. Interestingly, this aggregation phenomenon was also observed during Listeria monocytogenes interactions with Acanthamoeba and was termed ‘backpacking’ [18].…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Acanthamoebae was hypothesized to provide C. jejuni refuge [10], and indeed, we showed that Acanthamoebae spp. are a transient host for C. jejuni, and the bacterium is capable of subverting Acanthamoeba killing by employing similar survival strategies as it does in the cells of warm-blooded hosts [5,11]. Previously, we reported the inability of A. castellanii to phagocytose C. jejuni flagella mutants [11].…”

Section: Introductionmentioning

confidence: 99%

“…are a transient host for C. jejuni, and the bacterium is capable of subverting Acanthamoeba killing by employing similar survival strategies as it does in the cells of warm-blooded hosts [5,11]. Previously, we reported the inability of A. castellanii to phagocytose C. jejuni flagella mutants [11]. Here, we show that properties unrelated to motility function of flagella are crucial for A. castellanii interactions, and that the O-linked glycosylation modification of the flagellin facilitates recognition, capture and phagocytosis.…”

Section: Introductionmentioning

confidence: 99%

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Flagellin O-linked glycans are required for the interactions between Campylobacter jejuni and Acanthamoebae castellanii

Nasher,

Wren

2023

Microbiology

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The predation and engulfment of bacteria by Acanthamoebae facilitates intimate interactions between host and prey. This process plays an important and underestimated role in the physiology, ecology and evolution of pathogenic bacteria. Acanthamoebae species can be reservoirs for many important human pathogens including Campylobacter jejuni. C. jejuni is the leading cause of bacterial foodborne enteritis worldwide, despite being a microaerophile that is incapable of withstanding atmospheric levels of oxygen long-term. The persistence and transmission of this major pathogen in the natural environment outside its avian and mammalian hosts is not fully understood. Recent evidence has provided insight into the relationship of C. jejuni and Acanthamoebae spp. where Acanthamoebae are a transient host for this pathogen. Mutations to the flagella components were shown to affect C. jejuni–A. castellanii interactions. Here, we show that the motility function of flagella is not a prerequisite for C. jejuni–A. castellanii interactions and that specific O-linked glycan modifications of the C. jejuni major flagellin, FlaA, are important for the recognition, interaction and phagocytosis by A. castellanii. Substitution of the O-linked glycosylated serine 415 and threonine 477 with alanine within FlaA abolished C. jejuni interactions with A. castellanii and these mutants were indistinguishable from a ΔflaA mutant. By contrast, mutation to serine 405 did not affect C. jejuni 11168H and A. castellanii interactions. Given the abundance of flagella glycosylation among clinically important pathogens, our observations may have a wider implication for understanding host–pathogen interactions.

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“… C. jejuni 11168H flagella mutants abolished uptake by A. castellanii [11]. Here, live-cell imaging revealed that the C.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Flagellin O-linked glycans are required for the interactions between Campylobacter jejuni and Acanthamoebae castellanii

Nasher,

Wren

2023

Microbiology

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Acanthamoeba castellaniias a model for unveilingCampylobacter jejunihost-pathogen dynamics

Nasher,

Lehri,

Stabler

et al. 2024

Preprint

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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.

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Amoebae as training grounds for microbial pathogens

Price,

Hanford,

Al-Quadan

et al. 2024

mBio

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Grazing of amoebae on microorganisms represents one of the oldest predator-prey dynamic relationships in nature. It represents a genetic “melting pot” for an ancient and continuous multi-directional inter- and intra-kingdom horizontal gene transfer between amoebae and its preys, intracellular microbial residents, endosymbionts, and giant viruses, which has shaped the evolution, selection, and adaptation of microbes that evade degradation by predatory amoeba. Unicellular phagocytic amoebae are thought to be the ancient ancestors of macrophages with highly conserved eukaryotic processes. Selection and evolution of microbes within amoeba through their evolution to target highly conserved eukaryotic processes have facilitated the expansion of their host range to mammals, causing various infectious diseases. Legionella and environmental Chlamydia harbor an immense number of eukaryotic-like proteins that are involved in ubiquitin-related processes or are tandem repeats-containing proteins involved in protein-protein and protein-chromatin interactions. Some of these eukaryotic-like proteins exhibit novel domain architecture and novel enzymatic functions absent in mammalian cells, such as ubiquitin ligases, likely acquired from amoebae. Mammalian cells and amoebae may respond similarly to microbial factors that target highly conserved eukaryotic processes, but mammalian cells may undergo an accidental response to amoeba-adapted microbial factors. We discuss specific examples of microbes that have evolved to evade amoeba predation, including the bacterial pathogens— Legionella , Chlamydia , Coxiella, Rickettssia, Francisella, Mycobacteria , Salmonella, Bartonella , Rhodococcus , Pseudomonas, Vibrio , Helicobacter , Campylobacter , and Aliarcobacter . We also discuss the fungi Cryptococcus, and Asperigillus , as well as amoebae mimiviruses/giant viruses. We propose that amoeba-microbe interactions will continue to be a major “training ground” for the evolution, selection, adaptation, and emergence of microbial pathogens equipped with unique pathogenic tools to infect mammalian hosts. However, our progress will continue to be highly dependent on additional genomic, biochemical, and cellular data of unicellular eukaryotes.

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Survival of Campylobacter jejuni 11168H in Acanthamoebae castellanii Provides Mechanistic Insight into Host Pathogen Interactions

Cited by 5 publications

References 75 publications

Flagellin O-linked glycans are required for the interactions between Campylobacter jejuni and Acanthamoebae castellanii

Flagellin O-linked glycans are required for the interactions between Campylobacter jejuni and Acanthamoebae castellanii

Acanthamoeba castellaniias a model for unveilingCampylobacter jejunihost-pathogen dynamics

Amoebae as training grounds for microbial pathogens

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