Bacterial Persisters and Infection: Past, Present, and Progressing

2019 ◽  
Vol 73 (1) ◽  
pp. 359-385 ◽  
Author(s):  
Bridget Gollan ◽  
Grzegorz Grabe ◽  
Charlotte Michaux ◽  
Sophie Helaine

Persisters are nongrowing, transiently antibiotic-tolerant bacteria within a clonal population of otherwise susceptible cells. Their formation is triggered by environmental cues and involves the main bacterial stress response pathways that allow persisters to survive many harsh conditions, including antibiotic exposure. During infection, bacterial pathogens are exposed to a vast array of stresses in the host and form nongrowing persisters that survive both antibiotics and host immune responses, thereby most likely contributing to the relapse of many infections. While antibiotic persisters have been extensively studied over the last decade, the bulk of the work has focused on how these bacteria survive exposure to drugs in vitro. The ability of persisters to survive their interaction with a host is important yet underinvestigated. In order to tackle the problem of persistence of infections that contribute to the worldwide antibiotic resistance crisis, efforts should be made by scientific communities to understand and merge these two fields of research: antibiotic persisters and host-pathogen interactions. Here we give an overview of the history of the field of antibiotic persistence, report evidence for the importance of persisters in infection, and highlight studies that bridge the two areas.

2021 ◽  
Vol 11 (6) ◽  
pp. 564
Author(s):  
Chin-Man Wang ◽  
Keng-Poo Tan ◽  
Yeong-Jian Jan Wu ◽  
Jing-Chi Lin ◽  
Jian-Wen Zheng ◽  
...  

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10−115; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and HLA-B27 positivity (PFDR = 1.45 × 10−33; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.


Parasitology ◽  
1984 ◽  
Vol 88 (4) ◽  
pp. 575-577 ◽  
Author(s):  
N. A. Mitchison

Only a few years ago parasite immunology looked an unattractive subject better left to the dogged specialists. Parasites and hosts had been playing chess together for a million years, and there seemed little prospect of perturbing matters in favour of the host immune system. All that has changed, for three reasons. Firstly, we have learned how to grow at least some parasites in vitro, and prospects of doing so with others are encouraging. Secondly, progress in cellular immunology has revealed the sort of loopholes in the host defence system which parasites are likely to exploit: we are learning the questions which matter about parasites as antigens. Thirdly, and most importantly, molecular genetics is being brought to bear on parasites: we can now see a real, though long-term, prospect of manufacturing practicable vaccines through bio-engineering, and more immediately it gives us the tools needed to probe the host immune responses in the form of cloned antigens.


2020 ◽  
Vol 73 (4) ◽  
pp. 380
Author(s):  
John S. Albin ◽  
Bradley L. Pentelute

Organisms from all kingdoms of life have evolved a vast array of peptidic natural products to defend against microbes. These are known collectively as antimicrobial peptides (AMPs) or host defence peptides, reflecting their abilities not only to directly kill microbes, but also to modulate host immune responses. Despite decades of investigation, AMPs have yet to live up to their promise as lead therapeutics, a reality that reflects, in part, our incomplete understanding of these diverse agents in their various physiological contexts. Towards improving our understanding of AMP biology and the ways in which this can be best leveraged for therapeutic development, we are interested in large-scale comparisons of the antimicrobial and immunological activities of human AMPs, an undertaking that requires an efficient workflow for AMP synthesis and subsequent characterization. We describe here the application of flow chemistry and reverse-phase flash chromatography to the generation of 43AMPs, approaches that, when combined, significantly expedite synthesis and purification, potentially facilitating more systematic approaches to downstream testing and engineering.


2017 ◽  
Vol 22 (3) ◽  
pp. 318-322 ◽  
Author(s):  
Aditya K. Gupta ◽  
Jessie Carviel ◽  
Neil H. Shear

Onychomycosis is a chronic fungal infection that is recalcitrant to treatment and often results in relapse. New evidence suggests that disease prognosis may be linked to pathogens manipulating host immune responses. Therefore, individuals with specific mutations, including those affecting pattern recognition receptors or the interleukin (IL)–17 and IL-22 pathways, may be more susceptible to infection. Moreover, it is recommended that those with a family history of immune mutations or predisposition to fungal disease be treated aggressively for onychomycosis prior to symptom progression. In addition, incorporating genetic testing and new investigational therapy such as IL-33 and interferon-γ may improve treatment outcome.


2018 ◽  
Vol 27 (147) ◽  
pp. 170077 ◽  
Author(s):  
Shruthi Ravimohan ◽  
Hardy Kornfeld ◽  
Drew Weissman ◽  
Gregory P. Bisson

A past history of pulmonary tuberculosis (TB) is a risk factor for long-term respiratory impairment. Post-TB lung dysfunction often goes unrecognised, despite its relatively high prevalence and its association with reduced quality of life. Importantly, specific host and pathogen factors causing lung impairment remain unclear. Host immune responses probably play a dominant role in lung damage, as excessive inflammation and elevated expression of lung matrix-degrading proteases are common during TB. Variability in host genes that modulate these immune responses may determine the severity of lung impairment, but this hypothesis remains largely untested. In this review, we provide an overview of the epidemiological literature on post-TB lung impairment and link it to data on the pathogenesis of lung injury from the perspective of dysregulated immune responses and immunogenetics.


2008 ◽  
Vol 56 (4) ◽  
pp. 300-301
Author(s):  
Rachel Foster ◽  
Jennifer Carlring ◽  
Michael McKendrick ◽  
Ray Borrow ◽  
Edward Kaczmarski ◽  
...  

Parasitology ◽  
2010 ◽  
Vol 138 (2) ◽  
pp. 139-159 ◽  
Author(s):  
C. D. BOURKE ◽  
R. M. MAIZELS ◽  
F. MUTAPI

SUMMARYSimilarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recentin vitroand immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The ‘trade-off’ between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigensin utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations.


2021 ◽  
Author(s):  
Vivian Vasconcelos Costa ◽  
Michelle A Sugimoto ◽  
Josy Hubner ◽  
Caio S Bonilha ◽  
Celso Martins Queiroz-Junior ◽  
...  

Host immune responses contribute to dengue's pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, IFNα/βR-/-, AnxA1-/- and FPR2/ALX-/- mice were infected with Dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac2-26 for analysis. Additionally, the effect of Ac2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. While the absence of AnxA1 or its receptor FPR2/ALX aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestations. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease.


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