Chronic biofilm-based infections: skewing of the immune response

González, Juan F.; Hahn, Mark M.; Gunn, John S.

doi:10.1093/femspd/fty023

Cited by 95 publications

(84 citation statements)

References 55 publications

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“…The immune response against planktonic bacteria is very well studied for many different bacteria, including B. burgdorferi [71], but considerably less is known about the immune response to pathogenic biofilm [72]. Our positive IHC data for the presence of infiltrating T cells next to Borrelia aggregates suggest a connection between B. burgdorferi biofilm and the host inflammatory response and raise the question of what attracted the lymphocytes to the site of the biofilm.…”

Section: T-cell Inflammation Is Associated With Biofilmmentioning

confidence: 79%

The Long-Term Persistence of Borrelia burgdorferi Antigens and DNA in the Tissues of a Patient with Lyme Disease

et al. 2019

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Whether Borrelia burgdorferi, the causative agent of Lyme disease, can persist for long periods in the human body has been a controversial question. The objective of this study was to see if we could find B. burgdorferi in a Lyme disease patient after a long clinical course and after long-term antibiotic treatment. Therefore, we investigated the potential presence of B. burgdorferi antigens and DNA in human autopsy tissues from a well-documented serum-, PCR-, and culture-positive Lyme disease patient, a 53-year-old female from northern Westchester County in the lower Hudson Valley Region of New York State, who had received extensive antibiotic treatments during extensive antibiotic treatments over the course of her 16-year-long illness. We also asked what form the organism might take, with special interest in the recently found antibiotic-resistant aggregate form, biofilm. We also examined the host tissues for the presence of inflammatory markers such as CD3+ T lymphocytes. Autopsy tissue sections of the brain, heart, kidney, and liver were analyzed by histological and immunohistochemical methods (IHC), confocal microscopy, fluorescent in situ hybridization (FISH), polymerase chain reaction (PCR), and whole-genome sequencing (WGS)/metagenomics. We found significant pathological changes, including borrelial spirochetal clusters, in all of the organs using IHC combined with confocal microscopy. The aggregates contained a well-established biofilm marker, alginate, on their surfaces, suggesting they are true biofilm. We found B. burgdorferi DNA by FISH, polymerase chain reaction (PCR), and an independent verification by WGS/metagenomics, which resulted in the detection of B. burgdorferi sensu stricto specific DNA sequences. IHC analyses showed significant numbers of infiltrating CD3+ T lymphocytes present next to B. burgdorferi biofilms. In summary, we provide several lines of evidence that suggest that B. burgdorferi can persist in the human body, not only in the spirochetal but also in the antibiotic-resistant biofilm form, even after long-term antibiotic treatment. The presence of infiltrating lymphocytes in the vicinity of B. burgdorferi biofilms suggests that the organism in biofilm form might trigger chronic inflammation.

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Section: T-cell Inflammation Is Associated With Biofilmmentioning

confidence: 79%

The Long-Term Persistence of Borrelia burgdorferi Antigens and DNA in the Tissues of a Patient with Lyme Disease

et al. 2019

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“…Anti-tick immunity also increased the functional diversity and the importance of pathways involved in biofilm formation including colanic acid biosynthesis, a major component of bacterial biofilms [58]. Biofilm creates a favorable environment that increases antibiotic resistance, impairs host immunity, and increases tolerance to nutritional deprivation [59][60][61]. The formation of biofilms α (Figure 1a) due to increase in biofilm formers may be part of a protective response of the tick microbiota to anti-tick immunity.…”

Section: Discussionmentioning

confidence: 99%

Resistance of Tick Gut Microbiome to Anti-Tick Vaccines, Pathogen Infection and Antimicrobial Peptides

2020

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Ixodes scapularis ticks harbor microbial communities including pathogenic and non-pathogenic microbes. Pathogen infection increases the expression of several tick gut proteins, which disturb the tick gut microbiota and impact bacterial biofilm formation. Anaplasma phagocytophilum induces ticks to express I. scapularis antifreeze glycoprotein (IAFGP), a protein with antimicrobial activity, while Borrelia burgdorferi induces the expression of PIXR. Here, we tested the resistance of I. scapularis microbiome to A. phagocytophilum infection, antimicrobial peptide IAFGP, and anti-tick immunity specific to PIXR. We demonstrate that A. phagocytophilum infection and IAFGP affect the taxonomic composition and taxa co-occurrence networks, but had limited impact on the functional traits of tick microbiome. In contrast, anti-tick immunity disturbed the taxonomic composition and the functional profile of tick microbiome, by increasing both the taxonomic and pathways diversity. Mechanistically, we show that anti-tick immunity increases the representation and importance of the polysaccharide biosynthesis pathways involved in biofilm formation, while these pathways are under-represented in the microbiome of ticks infected by A. phagocytophilum or exposed to IAFGP. These analyses revealed that tick microbiota is highly sensitive to anti-tick immunity, while it is less sensitive to pathogen infection and antimicrobial peptides. Results suggest that biofilm formation may be a defensive response of tick microbiome to anti-tick immunity.

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“…Another bacterial phenotype that may contribute to a restrained immune response toward persistence is biofilm. Since adherent bacteria are not accessible for antibody opsonization and can block polymorphonuclear leukocyte signaling, several studies have shown the role of biofilms in skewing the T cell response, facilitating persistence (244).…”

Section: The Host Immune Response To Salmonella Persistencementioning

confidence: 99%

Persistent Infection and Long-Term Carriage of Typhoidal and Nontyphoidal Salmonellae

2018

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SUMMARY The ability of pathogenic bacteria to affect higher organisms and cause disease is one of the most dramatic properties of microorganisms. Some pathogens can establish transient colonization only, but others are capable of infecting their host for many years or even for a lifetime. Long-term infection is called persistence, and this phenotype is fundamental for the biology of important human pathogens, including Helicobacter pylori, Mycobacterium tuberculosis, and Salmonella enterica. Both typhoidal and nontyphoidal serovars of the species Salmonella enterica can cause persistent infection in humans; however, as these two Salmonella groups cause clinically distinct diseases, the characteristics of their persistent infections in humans differ significantly. Here, following a general summary of Salmonella pathogenicity, host specificity, epidemiology, and laboratory diagnosis, I review the current knowledge about Salmonella persistence and discuss the relevant epidemiology of persistence (including carrier rate, duration of shedding, and host and pathogen risk factors), the host response to Salmonella persistence, Salmonella genes involved in this lifestyle, as well as genetic and phenotypic changes acquired during prolonged infection within the host. Additionally, I highlight differences between the persistence of typhoidal and nontyphoidal Salmonella strains in humans and summarize the current gaps and limitations in our understanding, diagnosis, and curing of persistent Salmonella infections.

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Chronic biofilm-based infections: skewing of the immune response

Cited by 95 publications

References 55 publications

The Long-Term Persistence of Borrelia burgdorferi Antigens and DNA in the Tissues of a Patient with Lyme Disease

The Long-Term Persistence of Borrelia burgdorferi Antigens and DNA in the Tissues of a Patient with Lyme Disease

Resistance of Tick Gut Microbiome to Anti-Tick Vaccines, Pathogen Infection and Antimicrobial Peptides

Persistent Infection and Long-Term Carriage of Typhoidal and Nontyphoidal Salmonellae

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