-
Nature Chemical Biology Oct 2020Many bacterial pathogens secrete virulence factors, also known as effector proteins, directly into host cells. These effectors suppress pro-inflammatory host signaling... (Review)
Review
Many bacterial pathogens secrete virulence factors, also known as effector proteins, directly into host cells. These effectors suppress pro-inflammatory host signaling while promoting bacterial infection. A particularly interesting subset of effectors post-translationally modify host proteins using novel chemistry that is not otherwise found in the mammalian proteome, which we refer to as 'orthogonal post-translational modification' (oPTM). In this Review, we profile oPTM chemistry for effectors that catalyze serine/threonine acetylation, phosphate β-elimination, phosphoribosyl-linked ubiquitination, glutamine deamidation, phosphocholination, cysteine methylation, arginine N-acetylglucosaminylation, and glutamine ADP-ribosylation on host proteins. AMPylation, a PTM that could be considered orthogonal until only recently, is also discussed. We further highlight known cellular targets of oPTMs and their resulting biological consequences. Developing a complete understanding of oPTMs and the host cell processes they hijack will illuminate critical steps in the infection process, which can be harnessed for a variety of therapeutic, diagnostic, and synthetic applications.
Topics: Animals; Bacteria; Bacterial Proteins; Gene Expression Regulation, Bacterial; Host-Pathogen Interactions; Humans; Protein Processing, Post-Translational; Virulence
PubMed: 32943788
DOI: 10.1038/s41589-020-0638-2 -
International Journal of Molecular... Aug 2023is a devastating fungal pathogen that causes severe crop losses worldwide. It is of vital importance to understand its pathogenic mechanism for disease control. Through...
is a devastating fungal pathogen that causes severe crop losses worldwide. It is of vital importance to understand its pathogenic mechanism for disease control. Through a forward genetic screen combined with next-generation sequencing, a putative protein kinase, Cak1, was found to be involved in the growth and pathogenicity of . Knockout and complementation experiments confirmed that deletions in caused defects in mycelium and sclerotia development, as well as appressoria formation and host penetration, leading to complete loss of virulence. These findings suggest that Cak1 is essential for the growth, development, and pathogenicity of . Therefore, Cak1 could serve as a potential target for the control of infection through host-induced gene silencing (HIGS), which could increase crop resistance to the pathogen.
Topics: Virulence; Ascomycota; Gene Silencing; High-Throughput Nucleotide Sequencing
PubMed: 37628791
DOI: 10.3390/ijms241612610 -
Microbial Pathogenesis Aug 2022Aeromonas spp. is a pathogenic bacteria that potentially cause infection in farmed fish, including Catfishes. In the present study, dominant bacteria were isolated from...
Aeromonas spp. is a pathogenic bacteria that potentially cause infection in farmed fish, including Catfishes. In the present study, dominant bacteria were isolated from diseased Clarias magur and tentatively named BLBM-05. Based on morphological, physiological, and biochemical features as well as 16S rRNA gene sequence and gyrB gene sequences (Gen Bank accession number: MT973994.1 and MZ398017.1), the bacteria in the isolate was found to be Aeromonas caviae. Further, the isolate was screened for five known virulence genes, namely β-hemolysin, lafA, exu, ompA1 and ascV. Among them, three virulence genes related to pathogenicity, including aerolysin (aer), outer membrane protein (ompA1), lateral flagella (lafA), were identified in the A. caviae isolate. The median lethal dosage (LD) of the BLBM-05 isolate for magur was determined as 1.53x10 CFU/mL. The histopathological analysis showed that the BLBM-05 isolate induced considerable histological lesions in the magur fish, including necrosis, hemolysis of erythrocytes, myolysis, hemorrhage, and desquamation in the intestinal tissue, tissue loosening, and infiltration of inflammatory cells. Drug sensitivity test showed that the isolate was susceptible to Gentamicin, Ceftazidine, Ceftrioxone, Amikacin, Tetracycline, Meropener and Oxytetracycline. The present results provide a scientific basis to identify A. caviae further, a line of treatment for magur infected by this pathogen.
Topics: Aeromonas; Aeromonas caviae; Animals; Anti-Bacterial Agents; Gram-Negative Bacterial Infections; RNA, Ribosomal, 16S; Virulence
PubMed: 35781004
DOI: 10.1016/j.micpath.2022.105662 -
Microbiological Research Jan 2021Candida auris is a worrisome fungal pathogen of humans which emerged merely about a decade ago. Ever since then the scientific community worked hard to understand... (Review)
Review
Candida auris is a worrisome fungal pathogen of humans which emerged merely about a decade ago. Ever since then the scientific community worked hard to understand clinically relevant traits, such as virulence factors, antifungal resistance mechanisms, and its ability to adhere to human skin and medical devices. Whole-genome sequencing of clinical isolates and epidemiological studies outlining the path of nosocomial outbreaks have been the focus of research into this pathogenic and multidrug-resistant yeast since its first description in 2009. More recently, work was started by several laboratories to explore the biology of C. auris. Here, we review the insights of studies characterizing the mechanisms underpinning antifungal drug resistance, biofilm formation, morphogenetic switching, cell aggregation, virulence, and pathogenicity of C. auris. We conclude that, although some progress has been made, there is still a long journey ahead of us, before we fully understand this novel pathogen. Critically important is the development of molecular tools for C. auris to make this fungus genetically tractable and traceable. This will allow an in-depth molecular dissection of the life cycle of C. auris, of its characteristics while interacting with the human host, and the mechanisms it employs to avoid being killed by antifungals and the immune system.
Topics: Antifungal Agents; Biofilms; Candida; Candidiasis; Drug Resistance, Fungal; Fungi; Humans; Microbial Sensitivity Tests; Mutation; Phenotype; Transcriptome; Virulence; Virulence Factors; Whole Genome Sequencing
PubMed: 33096325
DOI: 10.1016/j.micres.2020.126621 -
Avian Pathology : Journal of the W.V.P.A Feb 2022Variant infectious bursal disease virus (vaIBDV) has been identified in various countries with significant economic losses. Recently, the first identification of a...
Variant infectious bursal disease virus (vaIBDV) has been identified in various countries with significant economic losses. Recently, the first identification of a variant strain in Malaysia was reported. The pathogenicities of the Malaysian variant, UPM1432/2019, and very virulent infectious bursal disease virus (vvIBDV), UPM1056/2018 strains were comparatively evaluated in specific-pathogen-free (SPF) chickens based on gross and histopathological examinations and viral load. Four-week-old SPF chickens were randomly divided into three groups; group 1 served as the control, while groups 2 and 3 birds were challenged with the vaIBDV and vvIBDV, respectively. Three birds from each group were weighed, euthanized and necropsied at 2, 3, 4, 5, 7 and 21 days post-challenge (dpc). Unlike UPM1056/2018 group, birds from UPM1432/2019 group did not show clinical signs or death. UPM1056/2018 strain caused 11% mortality rate in the infected chickens. The bursal body index (BBIX) for UPM1432/2019- and UPM1056/2018-infected groups was <0.7 from 2 dpc and continued to decrease to 0.49 and 0.45, respectively, at 21 dpc. UPM1432/2019 strain was more persistent in the bursa than UPM1056/2018 strain. Both strains induced similar pathological lesions in SPF chicks. These results indicate that the Malaysian vaIBDV severely damaged the immune organs of chickens and was more persistent in bursal tissue than vvIBDV. The study provides insight into the pathogenicity of the variant strain as further study may be required to evaluate the efficacy of the currently available IBD vaccines in Malaysia against the strain. RESEARCH HIGHLIGHTSEmerging Malaysian variant IBDV caused severe bursal damage without mortality.Atypical vvIBDV induced bursal atrophy with inflammatory response and caused low mortality.Malaysian variant IBDV was more persistent in bursal tissue than vvIBDV.
Topics: Animals; Birnaviridae Infections; Chickens; Infectious bursal disease virus; Poultry Diseases; Virulence
PubMed: 34842475
DOI: 10.1080/03079457.2021.2006604 -
The New Phytologist Oct 2020An understanding of the cell biology underlying the burgeoning molecular genetic and genomic knowledge of oomycete pathogenicity is essential to gain the full context of... (Review)
Review
An understanding of the cell biology underlying the burgeoning molecular genetic and genomic knowledge of oomycete pathogenicity is essential to gain the full context of how these pathogens cause disease on plants. An intense research focus on secreted Phytophthora effector proteins, especially those containing a conserved N-terminal RXLR motif, has meant that most cell biological studies into Phytophthora diseases have focussed on the effectors and their host target proteins. While these effector studies have provided novel insights into effector secretion and host defence mechanisms, there remain many unanswered questions about fundamental processes involved in spore biology, host penetration and haustorium formation and function.
Topics: Host-Pathogen Interactions; Phytophthora; Plant Diseases; Plants; Proteins; Virulence
PubMed: 32394464
DOI: 10.1111/nph.16650 -
Proceedings of the National Academy of... Nov 2023The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can...
The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can affect the health of humans as well as livestock. Here, we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis of , a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography, and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages of emerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation of and acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential of is yet to be fully realized.
Topics: Animals; Humans; Swine; Streptococcal Infections; Farms; Swine Diseases; Virulence; Streptococcus suis; Livestock
PubMed: 37963246
DOI: 10.1073/pnas.2307773120 -
Parasite Immunology Feb 2023We are constantly exposed to the threat of fungal infection. The outcome-clearance, commensalism or infection-depends largely on the ability of our innate immune... (Review)
Review
We are constantly exposed to the threat of fungal infection. The outcome-clearance, commensalism or infection-depends largely on the ability of our innate immune defences to clear infecting fungal cells versus the success of the fungus in mounting compensatory adaptive responses. As each seeks to gain advantage during these skirmishes, the interactions between host and fungal pathogen are complex and dynamic. Nevertheless, simply compromising the physiological robustness of fungal pathogens reduces their ability to evade antifungal immunity, their virulence, and their tolerance against antifungal therapy. In this article I argue that this physiological robustness is based on a 'Resilience Network' which mechanistically links and controls fungal growth, metabolism, stress resistance and drug tolerance. The elasticity of this network probably underlies the phenotypic variability of fungal isolates and the heterogeneity of individual cells within clonal populations. Consequently, I suggest that the definition of the fungal Resilience Network represents an important goal for the future which offers the clear potential to reveal drug targets that compromise drug tolerance and synergise with current antifungal therapies.
Topics: Antifungal Agents; Virulence; Host-Pathogen Interactions
PubMed: 35962618
DOI: 10.1111/pim.12946 -
Current Opinion in Microbiology Jun 2022Bacteria live in complex communities with multiple species and strains competing with each other. Victories and defeats within these microbial wars are largely ignored... (Review)
Review
Bacteria live in complex communities with multiple species and strains competing with each other. Victories and defeats within these microbial wars are largely ignored unless they have a noticeable impact on the environment or the host, for example when a disease causing strain emerges as a winner. Evolutionary theory typically explains pathogen emergence as a trade-off between virulence and transmissibility. However, for opportunistic pathogens the secondary infection niche is often a dead end, as the host is either killed or cured, so a trade-off can not develop. In this context it is difficult to explain the maintenance of virulence genes in the population as they would be costly. Here, current literature is synthesized to address this apparent conundrum. The potential for adaptations to one niche to provide a benefit in another is described for some pathogenic species and this paradigm is extended to include genetic diversity and competition among individual strains. Finally, considering assemblages of strains in fluctuating immune environments with complex micro-niche structure, a scenario is presented in which commensal organisms can be primed for invasive disease should the opportunity arise.
Topics: Adaptation, Physiological; Host-Pathogen Interactions; Virulence
PubMed: 35168173
DOI: 10.1016/j.mib.2022.01.009 -
Comparative Immunology, Microbiology... 2022Pasteurella multocida, the causative pathogen of rabbit pasteurellosis, causes significant economic losses in the commercial rabbit industry. However, the associated...
Pasteurella multocida, the causative pathogen of rabbit pasteurellosis, causes significant economic losses in the commercial rabbit industry. However, the associated pathogenic mechanism of P. multocida remains unclear. The aim of this study is to compare the genomes and pathogenicity of high- and low-virulence strains of P. multocida to advance the current understanding of rabbit pasteurellosis. The high-virulence strain rapidly proliferates in the lung and spleen of infected mice within approximately 9 h, maintaining a high bacterial load until host death. Meanwhile, the low-virulence strain only proliferates in mouse organs for a short time, with the bacterial load beginning to decrease 13 h post-infection. Moreover, the expressions of inflammatory cytokines MCP-1, TNF-α, and IL-1β are upregulated in all infected mouse lung and spleen tissue, however, the high-virulence strain induced significantly higher expression than the low-virulence strain. Histopathological analysis revealed greater inflammation and tissue lesions in the lung and spleen of mice infected with the high-virulence strain. Two pathogenicity-associated regions unique to the genome of the high-virulence strain harbor approximately 199 genes, including functional genes related to virulence factors, such as lipopolysaccharide biosynthesis, iron acquisition, biosynthesis of outer membrane proteins, and adhesion. These two genomic regions are shared by three previously sequenced, highly virulent P. multocida strains in rabbits. In conclusion, the increased pathogenicity of high-virulence P. multocida may be due to the presence of virulence-associated genes in two unique genomic regions, resulting in strong proliferative activity, significant inflammation, and pathological lesions in the mouse model. These findings provide important insights regarding the pathogenic mechanism underlying rabbit pasteurellosis.
Topics: Rabbits; Mice; Animals; Pasteurella multocida; Virulence; Pasteurella Infections; Virulence Factors; Inflammation
PubMed: 36306714
DOI: 10.1016/j.cimid.2022.101889