Hasil untuk "Microbiology"

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DOAJ Open Access 2025
Cpx‐mediated amino acid sensing diversifies gastrointestinal colonization of Klebsiella pneumoniae

Danyang Li, Qiucheng Shi, Liuqing He et al.

Abstract Klebsiella pneumoniae is a Gram‐negative opportunistic pathogenic bacterium that occasionally inhabits the human gastrointestinal tracts. Gut‐colonized K. pneumoniae may then metastasize to other organs and tissues, thus causing severe infections. In this study, we identified three cpxA mutations in K. pneumoniae that experimentally evolved to show reduced adhesive ability. CpxA is a sensor histidine kinase that rendered reduced surface adhesion and gut colonization ability in K. pneumoniae. Interestingly, one experimentally gained CpxA mutant (L168del) also commonly occurs in nature. K. pneumoniae containing CpxA variants showed different colonization potentials through altered type 3 fimbriae expression. Lastly, we demonstrated that CpxA contributes to amino acid sensing, thus regulating the colonization of K. pneumoniae both on solid surfaces and in mouse intestines. The polymorphism of CpxA may help to broaden the environmental adaptation of the bacterium. These findings together reveal a Cpx‐mediated regulation to diversify intestinal colonization in K. pneumoniae.

DOAJ Open Access 2025
Measles importations by international travelers, GeoSentinel 2019–2025

Ralph Huits, Dora Buonfrate, Kevin O'Laughlin et al.

Background: The global resurgence of measles is a threat to measles elimination campaigns. Measles importations by international travelers have been identified as a risk factor for outbreaks. Methods: We reviewed measles cases among international travelers and migrants reported to the GeoSentinel network. Results: From May 2019 through June 2025, GeoSentinel recorded 53 measles cases among travelers imported into 15 different countries. Travelers of all age groups were affected, and 74 % were 21 years or older. Thirty-three travelers (61 %) were hospitalized. Seventy-nine percent of cases reported no or unknown history of vaccination against measles. Conclusions: Against a background of increasing numbers of measles cases and outbreaks globally, GeoSentinel observed a stable trend of measles importations by international travelers. Measles caused considerable morbidity among travelers. Immunization effectively prevents measles in more than 97 % of individuals. Pretravel consultations provide an important opportunity to promote vaccination coverage for all vaccine-preventable diseases, including measles.

Arctic medicine. Tropical medicine, Infectious and parasitic diseases
DOAJ Open Access 2025
The Estimated Intake of S100B Relates to Microbiota Biodiversity in Different Diets

Tehreema Ghaffar, Veronica Volpini, Serena Platania et al.

The S100B protein, known for its role in the central and enteric nervous systems, has recently been identified in dietary sources such as milk, dairy products, fruits, and vegetables. Given its potential interaction with the gut microbiota, this study explores the relationship between dietary intake of S100B and microbiota biodiversity across different diets. A comprehensive study was conducted, estimating S100B concentrations in 13 dietary patterns recommended in different countries. This is the first study to provide a comparative estimation of S100B exposure from the diet and to explore its potential ecological and epidemiological relevance. The association between S100B levels and microbiota biodiversity was statistically analyzed, showing a direct correlation. Microbial diversity was assessed using the Shannon index, based on data extracted from studies reporting microbiota composition across dietary patterns. Additionally, the relative risk of Crohn’s disease was assessed in different populations to examine potential links between dietary patterns, S100B, and chronic disease prevention. A moderate positive correlation (R<sup>2</sup> = 0.537) was found between S100B concentration and Shannon index, suggesting that diets higher in S100B (e.g., Mediterranean diet) were associated with higher microbial alpha-diversity. Furthermore, Western-style diets, with the lowest S100B levels, exhibited a higher relative risk for Crohn’s disease (R<sup>2</sup> = 0.780). These findings highlight the potential role of dietary S100B content in modulating gut microbiota diversity and reducing chronic disease risk.

DOAJ Open Access 2025
Bacopa monnieri, a wonder plant in the backyard: Emphasizing the role of the microbiome in increasing its potential

Himani Barthwal, Charu Sharma, Vijay Kumar et al.

Recently, the utilization of natural or herbal products has increased worldwide. Various naturally isolated plant products have been assessed as therapeutics for the treatment of a variety of diseases. Microbes are related to medicinal plants and have enormous potential in the context of promoting plant growth traits and producing active ingredients of therapeutic importance. Bacopa monnieri, also called ‘Brahmi’ and water hyssop, has been utilized extensively in the ayurvedic system of medicine for a long time. Phytochemical investigations of B. monnieri extracts have revealed the occurrence of several active compounds, such as bacosides, alkaloids and triterpenoids. All these active chemical ingredients act as the best memory enhancer and are also used for various illnesses. The microbially mediated production of novel secondary metabolites with key biological activities could be an alternative method to obtain bioactive ingredients. This review highlights the interactions between microbes and the medicinal plant B. monnieri, illuminating the creation of biologically active compounds with medicinal importance within the plant.

Other systems of medicine
DOAJ Open Access 2024
Memory CD8 T cells are vulnerable to chronic IFN-γ signals but not to CD4 T cell deficiency in MHCII-deficient mice

Ruka Setoguchi, Tomoya Sengiku, Hiroki Kono et al.

Abstract The mechanisms by which the number of memory CD8 T cells is stably maintained remains incompletely understood. It has been postulated that maintaining them requires help from CD4 T cells, because adoptively transferred memory CD8 T cells persist poorly in MHC class II (MHCII)-deficient mice. Here we show that chronic interferon-γ signals, not CD4 T cell-deficiency, are responsible for their attrition in MHCII-deficient environments. Excess IFN-γ is produced primarily by endogenous colonic CD8 T cells in MHCII-deficient mice. IFN-γ neutralization restores the number of memory CD8 T cells in MHCII-deficient mice, whereas repeated IFN-γ administration or transduction of a gain-of-function STAT1 mutant reduces their number in wild-type mice. CD127high memory cells proliferate actively in response to IFN-γ signals, but are more susceptible to attrition than CD127low terminally differentiated effector memory cells. Furthermore, single-cell RNA-sequencing of memory CD8 T cells reveals proliferating cells that resemble short-lived, terminal effector cells and documents global downregulation of gene signatures of long-lived memory cells in MHCII-deficient environments. We propose that chronic IFN-γ signals deplete memory CD8 T cells by compromising their long-term survival and by diverting self-renewing CD127high cells toward terminal differentiation.

DOAJ Open Access 2024
Synergistic effects of the entomopathogenic fungus Isaria javanica and low doses of dinotefuran on the efficient control of the rice pest Sogatella furcifera

Tingting Zhou, Qian Zhao, Chengzhou Li et al.

The rice planthopper, Sogatella furcifera, is a piercing-sucking insect pest of rice, Oryza sativa. It is responsible for significant crop yield losses, and has developed moderate to high resistance to several commonly used chemical insecticides. We investigated the effects of the insect fungal pathogen Isaria javanica, alone and in combination with the chemical insecticide dinotefuran, on S. furcifera under both laboratory and field conditions. Our results show that I. javanica displays high infection efficiency and mortality for different stages of S. furcifera, reducing adult survival, female oviposition and ovary development. Laboratory bioassays showed that the combined use of I. javanica with a low dose (4–16 mg L–1) of dinotefuran resulted in higher mortality in S. furcifera than the use of I. javanica or dinotefuran alone. The combined treatment also had more significant effects on several host enzymes, including superoxide dismutase, catalase, peroxidase, and prophenol oxidase activities. In field trials, I. javanica effectively suppressed populations of rice planthoppers to low levels (22–64% of the level in untreated plots). Additional field experiments showed synergistic effects, i.e., enhanced efficiency, for the control of S. furcifera populations using the combination of a low dose of I. javanica (1×104 conidia mL–1) and a low dose of dinotefuran (~4.8–19.2% of normal field use levels), with control effects of >90% and a population level under 50 insects per 100 hills at 3–14 days post-treatment. Our findings indicate that the entomogenous fungus I. javanica offers an attractive biological control addition as part of the integrated pest management (IPM) practices for the control of rice plant pests.

Agriculture (General)
DOAJ Open Access 2024
Study on the correlation of supplementation with L-citrulline on the gastrointestinal flora and semen antifreeze performance of ram

Chen Fan, Chen Fan, Aikebaier Aihemaiti et al.

IntroductionCryopreservation of semen can give full play to the reproductive advantages of male animals. However, in actual production, due to the poor frost resistance of sheep semen and the low conception rate, the promotion of sheep frozen semen is greatly hindered. Therefore, it is urgent to improve the frost resistance of semen to improve the quality of frozen semen. At present, most studies on improving the quality of frozen semen are based on the improvement of semen dilutions, and few studies on improving the freezing resistance of ram semen by feeding functional amino acids.MethodsTherefore, 24 Turpan black rams were divided into high antifreeze group (HF) and a low antifreeze group (LF) Each of these groups was further randomly divided into control and experimental subgroups. The control subgroup was fed a basal diet, while the experimental subgroup received an additional 12 g/d of L-Cit supplementation based on the control group for a duration of 90 days.ResultsThe results showed that Following L-Cit supplementation, the experimental group demonstrated significantly elevated sperm density and VSL (Velocity of straight line), T-AOC, GSH-Px, and NO levels in fresh semen compared to the control group (P &lt; 0.01). After thawing, the experimental group exhibited significantly higher levels of T-AOC, GSH-Px, and NO compared to the control group (P &lt; 0.01). Additionally, the HFT group, after thawing frozen semen, displayed significantly higher HK1 protein expression compared to the control group. The number of spermatogonia, spermatocytes, and sperm cells in the HFT group was significantly higher than that in the HFC group. Moreover, 16S rRNA sequence analysis showed that Candidatus_Saccharimonas, Staphylococcus, Weissella, succinivbrionaceae_UcG_002, and Quinella were significantly enriched in the rumen of the HFT group, while Ureaplasma was significantly enriched in the HFC group. In the duodenum, Clostridiales_bacterium_Firm_14, Butyrivibrio, and Prevotellaceae_NK3831_group were significantly enriched in the HFT group, whereas Desulfovibrio and Quinella were significantly enriched in the HFC group.DiscussionUnder the conditions employed in this study, L-Cit supplementation was found to enhance the intestinal flora composition in rams, thereby improving semen quality, enhancing the antifreeze performance of semen, and promoting the development of testicular spermatogenic cells.

DOAJ Open Access 2024
Genital Warts in Women Vaccinated against HPV in Childhood: A Systematic Review

Renata Malheiro, César Magalhães, Cláudia Camila Dias et al.

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection among young women. Notably, more than ten years after the introduction of HPV vaccination programs in Europe, it is essential to review the real-world evidence of the incidence of anogenital warts (GWs) among women vaccinated during childhood. In this systematic review, three databases were searched for studies published between January 2008 and September 2023. Nine cohort studies were included. A total of 890,320 HPV-vaccinated women and 1,922,033 unvaccinated women were evaluated. All the studies but one investigated the 4vHPV vaccine. The incidence rate of GWs in vaccinated women ranged from 0.0 to 1650 per 100,000 person-years. The highest incidence rates were found in women vaccinated with one dose at the age of 17–19 years old and in fully vaccinated women only after 19 years of age. Similar incidence values were reported among unvaccinated women. The incidence of GWs was lower when the age at first dose was 9–11 years old. This systematic review reveals that the incidence of GWs among HPV-vaccinated women is related to the age of vaccination and the number of vaccine doses received. In the post-vaccination era, epidemiological surveillance of the incidence of GWs and their genotypes is crucial.

DOAJ Open Access 2022
Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention

Madubuike Umunna Anyanwu, Obichukwu Chisom Nwobi, Charles Odilichukwu R. Okpala et al.

Mobile tigecycline resistance (MTR) threatens the clinical efficacy of the salvage antibiotic, tigecycline (TIG) used in treating deadly infections in humans caused by superbugs (multidrug-, extensively drug-, and pandrug-resistant bacteria), including carbapenem- and colistin-resistant bacteria. Currently, non-mobile tet(X) and mobile plasmid-mediated transmissible tet(X) and resistance-nodulation-division (RND) efflux pump tmexCD-toprJ genes, conferring high-level TIG (HLT) resistance have been detected in humans, animals, and environmental ecosystems. Given the increasing rate of development and spread of plasmid-mediated resistance against the two last-resort antibiotics, colistin (COL) and TIG, there is a need to alert the global community on the emergence and spread of plasmid-mediated HLT resistance and the need for nations, especially developing countries, to increase their antimicrobial stewardship. Justifiably, MTR spread projects One Health ramifications and portends a monumental threat to global public and animal health, which could lead to outrageous health and economic impact due to limited options for therapy. To delve more into this very important subject matter, this current work will discuss why MTR is an emerging health catastrophe requiring urgent One Health global intervention, which has been constructed as follows: (a) antimicrobial activity of TIG; (b) mechanism of TIG resistance; (c) distribution, reservoirs, and traits of MTR gene-harboring isolates; (d) causes of MTR development; (e) possible MTR gene transfer mode and One Health implication; and (f) MTR spread and mitigating strategies.

DOAJ Open Access 2022
AMPK Is Involved in Regulating the Utilization of Carbon Sources, Conidiation, Pathogenicity, and Stress Response of the Nematode-Trapping Fungus Arthrobotrys oligospora

Wenjie Wang, Yining Zhao, Na Bai et al.

ABSTRACT AMP-activated protein kinase (AMPK), a heterotrimeric complex, can sense energy and nutritional status in eukaryotic cells, thereby participating in the regulation of multiple cellular processes. In this study, we characterized the function of the catalytic α-subunit (SNF1) and the two regulatory β- and γ-subunits (GAL83 and SNF4) of AMPK in a representative nematode-trapping fungus, Arthrobotrys oligospora, by gene knockout, phenotypic analysis, and RNA sequencing. The ability of the AMPK complex mutants (including ΔAosnf1, ΔAogal83, and ΔAosnf4) to utilize a nonfermentable carbon source (glycerol) was reduced, and the spore yields and trap formation were remarkably decreased. Moreover, AMPK plays an important role in regulating stress response and nematode predation efficiency. Transcriptomic profiling between the wild-type strain and ΔAosnf1 showed that differentially expressed genes were enriched for peroxisome, endocytosis, fatty acid degradation, and multilipid metabolism (sphingolipid, ether lipid, glycerolipid, and glycerophospholipid). Meanwhile, a reduced lipid droplet accumulation in ΔAosnf1, ΔAogal83, and ΔAosnf4 mutants was observed, and more vacuoles appeared in the mycelia of the ΔAosnf1 mutant. These results highlight the important regulatory role of AMPK in the utilization of carbon sources and lipid metabolism, as well as providing novel insights into the regulatory mechanisms of the mycelia development, conidiation, and trap formation of nematode-trapping (NT) fungi. IMPORTANCE NT fungi are widely distributed in various ecosystems and are important factors in the control of nematode populations in nature; their trophic mycelia can form unique infectious devices (traps) for capturing nematodes. Arthrobotrys oligospora is a representative NT fungi which can develop complex three-dimensional networks (adhesive networks) for nematode predation. Here, we demonstrated that AMPK plays an important role in the glycerol utilization, conidiation, trap formation, and nematode predation of A. oligospora, which was further confirmed by transcriptomic analysis of the wild-type and mutant strains. In particular, our analysis indicated that AMPK is required for lipid metabolism, which is primarily associated with energy regulation and is essential for trap formation. Therefore, this study extends the functional study of AMPK in NT fungi and helps to elucidate the molecular mechanism of the regulation of trap development, as well as laying the foundation for the development of efficient nematode biocontrol agents.

DOAJ Open Access 2021
Dangerous Liaisons: Long-Term Replication with an Extrachromosomal HPV Genome

Alix Warburton, Ashley N. Della Fera, Alison A. McBride

Papillomaviruses cause persistent, and usually self-limiting, infections in the mucosal and cutaneous surfaces of the host epithelium. However, in some cases, infection with an oncogenic HPV can lead to cancer. The viral genome is a small, double-stranded circular DNA molecule that is assembled into nucleosomes at all stages of infection. The viral minichromosome replicates at a low copy number in the nucleus of persistently infected cells using the cellular replication machinery. When the infected cells differentiate, the virus hijacks the host DNA damage and repair pathways to replicate viral DNA to a high copy number to generate progeny virions. This strategy is highly effective and requires a close association between viral and host chromatin, as well as cellular processes associated with DNA replication, repair, and transcription. However, this association can lead to accidental integration of the viral genome into host DNA, and under certain circumstances integration can promote oncogenesis. Here we describe the fate of viral DNA at each stage of the viral life cycle and how this might facilitate accidental integration and subsequent carcinogenesis.

DOAJ Open Access 2021
Major genetic discontinuity and novel toxigenic species in Clostridioides difficile taxonomy

Daniel R Knight, Korakrit Imwattana, Brian Kullin et al.

Clostridioides difficile infection (CDI) remains an urgent global One Health threat. The genetic heterogeneity seen across C. difficile underscores its wide ecological versatility and has driven the significant changes in CDI epidemiology seen in the last 20 years. We analysed an international collection of over 12,000 C. difficile genomes spanning the eight currently defined phylogenetic clades. Through whole-genome average nucleotide identity, and pangenomic and Bayesian analyses, we identified major taxonomic incoherence with clear species boundaries for each of the recently described cryptic clades CI–III. The emergence of these three novel genomospecies predates clades C1–5 by millions of years, rewriting the global population structure of C. difficile specifically and taxonomy of the Peptostreptococcaceae in general. These genomospecies all show unique and highly divergent toxin gene architecture, advancing our understanding of the evolution of C. difficile and close relatives. Beyond the taxonomic ramifications, this work may impact the diagnosis of CDI.

Medicine, Science
DOAJ Open Access 2018
Serotypes With Low Invasive Potential Are Associated With an Impaired Antibody Response in Invasive Pneumococcal Disease

Nils Littorin, Fabian Uddén, Jonas Ahl et al.

Pneumococcal polysaccharide vaccines may elicit a hyporesponse under certain conditions. There is limited knowledge, however, on the type of specific antibody response in individuals with invasive pneumococcal disease (IPD). The aim of this study was to investigate the functional antibody response in patients with IPD caused by different serotypes. Pre-immune and convalescent sera from 40 patients (age 14–91 years) with IPD caused by serotypes with low (serotype 3, 19F, and 23F) and high (1, 4, 7F, and 14) invasive potential were investigated. For each patient, the homologous serotype-specific antibody concentration was determined. The functionality of induced antibodies post-IPD was evaluated in an opsonophagocytic assay (OPA). Undetectable or decreased pneumococcal killing in OPA following IPD, i.e., a nonfunctional antibody response, was observed in 24 of 40 patients (60%). Patients with nonfunctional antibody responses had lower serotype specific IgG antibody ratios post-IPD than patients with increased OPA titres. A nonfunctional antibody response was associated with low invasive serotypes (3, 19F, and 23F, p = 0.015). In conclusion, a nonfunctional antibody response may follow IPD, and was in our cohort associated to serotypes with low invasive potential. These findings need to be confirmed in a larger material.

DOAJ Open Access 2018
Variable Domain N-Linked Glycans Acquired During Antigen-Specific Immune Responses Can Contribute to Immunoglobulin G Antibody Stability

Fleur S. van de Bovenkamp, Fleur S. van de Bovenkamp, Ninotska I. L. Derksen et al.

Immunoglobulin G (IgG) can contain N-linked glycans in the variable domains, the so-called Fab glycans, in addition to the Fc glycans in the CH2 domains. These Fab glycans are acquired following introduction of N-glycosylation sites during somatic hypermutation and contribute to antibody diversification. We investigated whether Fab glycans may—in addition to affecting antigen binding—contribute to antibody stability. By analyzing thermal unfolding profiles of antibodies with or without Fab glycans, we demonstrate that introduction of Fab glycans can improve antibody stability. Strikingly, removal of Fab glycans naturally acquired during antigen-specific immune responses can deteriorate antibody stability, suggesting in vivo selection of stable, glycosylated antibodies. Collectively, our data show that variable domain N-linked glycans acquired during somatic hypermutation can contribute to IgG antibody stability. These findings indicate that introducing Fab glycans may represent a mechanism to improve therapeutic/diagnostic antibody stability.

Immunologic diseases. Allergy
DOAJ Open Access 2017
The Absence of NOD1 Enhances Killing of Aspergillus fumigatus Through Modulation of Dectin-1 Expression

Mark S. Gresnigt, Mark S. Gresnigt, Martin Jaeger et al.

One of the major life-threatening infections for which severely immunocompromised patients are at risk is invasive aspergillosis (IA). Despite the current treatment options, the increasing antifungal resistance and poor outcome highlight the need for novel therapeutic strategies to improve outcome of patients with IA. In the current study, we investigated whether and how the intracellular pattern recognition receptor NOD1 is involved in host defense against Aspergillus fumigatus. When exploring the role of NOD1 in an experimental mouse model, we found that Nod1−/− mice were protected against IA and demonstrated reduced fungal outgrowth in the lungs. We found that macrophages derived from bone marrow of Nod1−/− mice were more efficiently inducing reactive oxygen species and cytokines in response to Aspergillus. Most strikingly, these cells were highly potent in killing A. fumigatus compared with wild-type cells. In line, human macrophages in which NOD1 was silenced demonstrated augmented Aspergillus killing and NOD1 stimulation decreased fungal killing. The differentially altered killing capacity of NOD1 silencing versus NOD1 activation was associated with alterations in dectin-1 expression, with activation of NOD1 reducing dectin-1 expression. Furthermore, we were able to demonstrate that Nod1−/− mice have elevated dectin-1 expression in the lung and bone marrow, and silencing of NOD1 gene expression in human macrophages increases dectin-1 expression. The enhanced dectin-1 expression may be the mechanism of enhanced fungal killing of Nod1−/− cells and human cells in which NOD1 was silenced, since blockade of dectin-1 reversed the augmented killing in these cells. Collectively, our data demonstrate that NOD1 receptor plays an inhibitory role in the host defense against Aspergillus. This provides a rationale to develop novel immunotherapeutic strategies for treatment of aspergillosis that target the NOD1 receptor, to enhance the efficiency of host immune cells to clear the infection by increasing fungal killing and cytokine responses.

Immunologic diseases. Allergy
DOAJ Open Access 2016
Tree species richness, diversity, and regeneration status in different oak (Quercus spp.) dominated forests of Garhwal Himalaya, India

Sushma Singh, Zubair A. Malik, Chandra M. Sharma

Himalayan forests are dominated by different species of oaks (Quercus spp.) at different altitudes. These oaks are intimately linked with hill agriculture as they protect soil fertility, watershed, and local biodiversity. They also play an important role in maintaining ecosystem stability. This work was carried out to study the diversity and regeneration status of some oak forests in Garhwal Himalaya, India. A total of 18 tree species belonging to 16 genera and 12 families were reported from the study area. Species richness varied for trees (4–7), saplings (3–10), and seedlings (2–6). Seedling and sapling densities (Ind/ha) varied between 1,376 Ind/ha and 9,600 Ind/ha and 167 Ind/ha and 1,296 Ind/ha, respectively. Species diversity varied from 1.27 to 1.86 (trees), from 0.93 to 3.18 (saplings), and from 0.68 to 2.26 (seedlings). Total basal area (m2/ha) of trees and saplings was 2.2–87.07 m2/ha and 0.20–2.24 m2/ha, respectively, whereas that of seedlings varied from 299 cm2/ha to 8,177 cm2/ha. Maximum tree species (20–80%) had “good” regeneration. Quercus floribunda, the dominant tree species in the study area, showed “poor” regeneration, which is a matter of concern, and therefore, proper management and conservation strategies need to be developed for maintenance and sustainability of this oak species along with other tree species that show poor or no regeneration.

DOAJ Open Access 2012
Host epithelial cell invasion by Campylobacter jejuni: trigger or zipper mechanism?

Tadhg eÓ Cróinín, Steffen eBackert

Campylobacter jejuni, a spiral-shaped Gram-negative pathogen, is a highly frequent cause of gastrointestinal foodborne illness in humans worldwide. Clinical outcome of C. jejuni infections ranges from mild to severe diarrheal disease, and some other complications including reactive arthritis and Guillain–Barr&#233; syndrome. This review article highlights various C. jejuni pathogenicity factors, host cell determinants and proposed signaling mechanisms involved in human host cell invasion and their potential role in the development of C. jejuni-mediated disease. A model is presented which outlines the various important interactions of C. jejuni with the intestinal epithelium, and we discuss the pro’s and con’s for the zipper over the trigger mechanism of invasion. Future work should clarify the contradictory role of some previously identified factors, and should identify and characterize novel virulence determinants, which are crucial to provide fresh insights into the diversity of strategies employed by this pathogen to cause disease.

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