Immunity of fleas (Order Siphonaptera)

Brown, Lawrence Parmly

doi:10.1016/j.dci.2019.03.019

Cited by 14 publications

(15 citation statements)

References 45 publications

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“…Although trypsin and chymotrypsin are primarily considered blood feeding-associated molecules, the presence of ingested pathogens seems to modulate their abundance (Brown, 2019). In our study, serine proteases were associated with the B. henselae infection status of C. felis, suggesting an additional role in the flea immune response, as previously reported (Dreher-Lesnick et al, 2010;Brown, 2019;Bland et al, 2020).…”

Section: Serine Proteasessupporting

confidence: 80%

“…Similar to several other blood-sucking insects, C. felis has a plethora of serine proteases (Gaines et al, 1999), which play a role in numerous biological processes, including but not restricted to zymogen activation and digestion. Indeed, serine proteases (trypsin and chymotrypsin) represent the most abundant digestive enzymes in fleas (Gaines et al, 1999;Dreher-Lesnick et al, 2010;Greene et al, 2015;Brown, 2019;Bland et al, 2020). These proteases convert proteins into smaller peptides and represent the most common digestive enzymes in blood-feeding arthropods (Bland et al, 2020).…”

Section: Serine Proteasesmentioning

confidence: 99%

“…A vaccine targeting both flea fitness and pathogen competence is an attractive choice requiring the identification of flea proteins/metabolites with a dual effect. Even though recent developments in vector and pathogen omics have advanced the understanding of the genetic factors and molecular pathways involved at the tickpathogen interface, leading to discovery of candidate protective antigens (de la Fuente et al, 2007a;de la Fuente et al, 2007b), only a few studies have focused on the interaction between fleas and flea-borne pathogens (Dreher-Lesnick et al, 2010;Brown, 2019;Bland et al, 2020;Danchenko et al, 2021;Laukaitis and Macaluso, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Using Proteomic Approaches to Unravel the Response of Ctenocephalides felis felis to Blood Feeding and Infection With Bartonella henselae

André

Neupane

Lappin

et al. 2022

Front. Cell. Infect. Microbiol.

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Among the Ctenocephalides felis felis-borne pathogens, Bartonella henselae, the main aetiological agent of cat scratch disease (CSD), is of increasing comparative biomedical importance. Despite the importance of B. henselae as an emergent pathogen, prevention of the diseases caused by this agent in cats, dogs and humans mostly relies on the use of ectoparasiticides. A vaccine targeting both flea fitness and pathogen competence is an attractive choice requiring the identification of flea proteins/metabolites with a dual effect. Even though recent developments in vector and pathogen -omics have advanced the understanding of the genetic factors and molecular pathways involved at the tick-pathogen interface, leading to discovery of candidate protective antigens, only a few studies have focused on the interaction between fleas and flea-borne pathogens. Taking into account the period of time needed for B. henselae replication in flea digestive tract, the present study investigated flea-differentially abundant proteins (FDAP) in unfed fleas, fleas fed on uninfected cats, and fleas fed on B. henselae-infected cats at 24 hours and 9 days after the beginning of blood feeding. Proteomics approaches were designed and implemented to interrogate differentially expressed proteins, so as to gain a better understanding of proteomic changes associated with the initial B. henselae transmission period (24 hour timepoint) and a subsequent time point 9 days after blood ingestion and flea infection. As a result, serine proteases, ribosomal proteins, proteasome subunit α-type, juvenile hormone epoxide hydrolase 1, vitellogenin C, allantoinase, phosphoenolpyruvate carboxykinase, succinic semialdehyde dehydrogenase, glycinamide ribotide transformylase, secreted salivary acid phosphatase had high abundance in response of C. felis blood feeding and/or infection by B. henselae. In contrast, high abundance of serpin-1, arginine kinase, ribosomal proteins, peritrophin-like protein, and FS-H/FSI antigen family member 3 was strongly associated with unfed cat fleas. Findings from this study provide insights into proteomic response of cat fleas to B. henselae infected and uninfected blood meal, as well as C. felis response to invading B. henselae over an infection time course, thus helping understand the complex interactions between cat fleas and B. henselae at protein levels.

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Section: Serine Proteasessupporting

confidence: 80%

Section: Serine Proteasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Using Proteomic Approaches to Unravel the Response of Ctenocephalides felis felis to Blood Feeding and Infection With Bartonella henselae

André

Neupane

Lappin

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Drosophila and Galleria mellonella have recently been adapted as models for Y. pestisinsect interactions and have been used to show that the bacterial PhoPQ two-component gene regulatory system and the OxyR transcription factor mediate resistance to AMPs and ROS and are required for colonization of Drosophila and Galleria larvae, as well as the rat flea gut [8,17,18]. In studies of flea physiology and genetics, primarily with the cat flea, Ctenocephalides felis, many canonical insect responses to pathogens have been observed [7,[19][20][21][22]. Recent studies using cultured Drosophila cells and RNA interference in cat fleas indicate that R. typhi infection is moderated by antimicrobials generated by the immune deficiency (IMD) pathway, the major insect innate immune cascade that detects and responds to DAP-type peptidoglycan, common in Gram-negative bacteria [19].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Transcriptomic profiling of the digestive tract of the rat flea, Xenopsylla cheopis, following blood feeding and infection with Yersinia pestis

et al. 2020

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Yersinia pestis, the causative agent of plague, is a highly lethal pathogen transmitted by the bite of infected fleas. Once ingested by a flea, Y. pestis establish a replicative niche in the gut and produce a biofilm that promotes foregut colonization and transmission. The rat flea Xenopsylla cheopis is an important vector to several zoonotic bacterial pathogens including Y. pestis. Some fleas naturally clear themselves of infection; however, the physiological and immunological mechanisms by which this occurs are largely uncharacterized. To address this, RNA was extracted, sequenced, and distinct transcript profiles were assembled de novo from X. cheopis digestive tracts isolated from fleas that were either: 1) not fed for 5 days; 2) fed sterile blood; or 3) fed blood containing~5x10 8 CFU/ml Y. pestis KIM6+. Analysis and comparison of the transcript profiles resulted in identification of 23 annotated (and 11 unknown or uncharacterized) digestive tract transcripts that comprise the early transcriptional response of the rat flea gut to infection with Y. pestis. The data indicate that production of antimicrobial peptides regulated by the immune-deficiency pathway (IMD) is the primary flea immune response to infection with Y. pestis. The remaining infection-responsive transcripts, not obviously associated with the immune response, were involved in at least one of 3 physiological themes: 1) alterations to chemosensation and gut peristalsis; 2) modification of digestion and metabolism; and 3) production of chitin-binding proteins (peritrophins). Despite producing several peritrophin transcripts shortly after feeding, including a subset that were infection-responsive, no thick peritrophic membrane was detectable by histochemistry or electron microscopy of rat flea guts for the first 24 hours following blood-feeding. Here we discuss the physiological implications of rat flea infection-responsive transcripts, the function of X. cheopis peritrophins, and the mechanisms by which Y. pestis may be cleared from the flea gut.

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“…Fleas are the major vector of other significant zoonotic bacterial diseases, such as murine typhus (Rickettsia typhi) and cat-scratch disease (Bartonella henselae) [9]. Nonetheless, little is known about the innate immune responses of Siphonapteran insects [10].…”

Section: Introductionmentioning

confidence: 99%

Yersinia pestis lipopolysaccharide remodeling confers resistance to a Xenopsylla cheopis cecropin

Mathew

Aoyagi

Fisher

2021

Preprint

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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.

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Immunity of fleas (Order Siphonaptera)

Cited by 14 publications

References 45 publications

Using Proteomic Approaches to Unravel the Response of Ctenocephalides felis felis to Blood Feeding and Infection With Bartonella henselae

Using Proteomic Approaches to Unravel the Response of Ctenocephalides felis felis to Blood Feeding and Infection With Bartonella henselae

Transcriptomic profiling of the digestive tract of the rat flea, Xenopsylla cheopis, following blood feeding and infection with Yersinia pestis

Yersinia pestis lipopolysaccharide remodeling confers resistance to a Xenopsylla cheopis cecropin

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