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Unveiling the dance of evolution: Pla-mediated cleavage of Ymt modulates the virulence dynamics of .MBio Jul 2024has recently evolved into a highly lethal flea-borne pathogen through the pseudogenization of extensive genes and the acquisition of exogenous plasmids. Particularly...
UNLABELLED
has recently evolved into a highly lethal flea-borne pathogen through the pseudogenization of extensive genes and the acquisition of exogenous plasmids. Particularly noteworthy are the newly acquired pPCP1 and pMT1 plasmids, which encode the virulence determinants Pla and murine toxin (Ymt), crucial for subcutaneous infection and survival within flea vector of , respectively. This study reveals that Pla can cleave Ymt at K299 both and expressing Ymt displays enhanced biofilm formation and increased blood survival, indicating significant roles of Pla-mediated Ymt cleavage in these phenotypes. Intriguingly, although both the ancestral form of Pla and the prevalent Pla-I259T variant in modern strains are capable of cleaving Ymt at K299, the cleavage efficiency of Pla-I259T is only half that of the ancestral variant. In subcutaneous infection, mice infected with ΔK299A show significantly prolonged survival compared to those infected with Δ. Similarly, infection with ΔI259T also results in extended survival compared to Δ infection. These data demonstrate that the I259T substitution of Pla mitigates the enhanced virulence of in mice caused by Pla-mediated Ymt cleavage, thereby prolonging the survival period of infected animals and potentially conferring advantages on the transmission of to the next host. These findings deepen our understanding of the intricate interplay between two newly acquired plasmids and shed light on the positive selection of the Pla-I259T mutation, providing new insights into the virulence dynamics and transmission mechanisms of .
IMPORTANCE
The emergence of as a highly lethal pathogen is driven by extensive gene pseudogenization and acquisition of exogenous plasmids pPCP1 and pMT1. However, the interplay between these two plasmids during evolution remains largely unexplored. Our study reveals intricate interactions between Ymt and Pla, two crucial virulence determinants encoded on these plasmids. Pla-mediated cleavage of Ymt significantly decreases survival in mouse blood and enhances its virulence in mice. The prevalent Pla-I259T variant in modern strains displays reduced Ymt cleavage, thereby extending the survival of infected animals and potentially increasing strain transmissibility. Our findings shed light on the nuanced evolution of , wherein reduced cleavage efficiency is a positive selection force, shaping the pathogen's natural trajectory.
PubMed: 38958447
DOI: 10.1128/mbio.01075-24 -
MBio Jul 2024is a Gram-negative gastrointestinal pathogen responsible for the diarrheal disease cholera. Expression of key virulence factors, cholera toxin and toxin-coregulated...
UNLABELLED
is a Gram-negative gastrointestinal pathogen responsible for the diarrheal disease cholera. Expression of key virulence factors, cholera toxin and toxin-coregulated pilus, is regulated directly by ToxT and indirectly by two transmembrane transcription regulators (TTRs), ToxR and TcpP, that promote the expression of . TcpP abundance and activity are controlled by TcpH, a single-pass transmembrane protein, which protects TcpP from a two-step proteolytic process known as regulated intramembrane proteolysis (RIP). The mechanism of TcpH-mediated protection of TcpP represents a major gap in our understanding of pathogenesis. The absence of leads to unimpeded degradation of TcpP and a colonization defect in a neonate mouse model of colonization. Here, we show that TcpH protects TcpP from RIP direct interaction. We also demonstrate that α-linolenic acid, a dietary fatty acid, promotes TcpH-dependent inhibition of RIP co-association of TcpP and TcpH molecules within detergent-resistant membranes (DRMs) in a mechanism requiring the TcpH transmembrane domain. Taken together, our data support a model where cells use exogenous α-linolenic acid to remodel the phospholipid bilayer , leading to co-association of TcpP and TcpH within DRMs where RIP of TcpP is inhibited by TcpH, thereby promoting pathogenicity.
IMPORTANCE
continues to pose a significant global burden on health and an alternative therapeutic approach is needed, due to evolving multidrug resistance strains. Transcription of , stimulated by TcpP and ToxR, is essential for pathogenesis. Our results show that TcpP, one of the major regulators of gene expression, is protected from proteolysis by TcpH, direct interaction. Furthermore, we identified a gut metabolite, α-linolenic acid, that stimulates the co-association of TcpP and TcpH within detergent-resistant membranes (also known as lipid-ordered membrane domains), thereby supporting TcpH-dependent antagonism of TcpP proteolysis. Data presented here extend our knowledge of RIP, virulence gene regulation in , and, to the best of our knowledge, provides the first evidence that lipid-ordered membranes exist within . The model presented here also suggests that TTRs, common among bacteria and archaea, and co-component signal transduction systems present in , could also be influenced similarly.
PubMed: 38958446
DOI: 10.1128/mbio.00721-24 -
MBio Jul 2024The physiology and ecology of particle-associated marine bacteria are of growing interest, but our knowledge of their aggregation behavior and mechanisms controlling...
UNLABELLED
The physiology and ecology of particle-associated marine bacteria are of growing interest, but our knowledge of their aggregation behavior and mechanisms controlling their association with particles remains limited. We have found that a particle-associated isolate, sp. ALT199 strain 4B03, and the related type-strain 27126 both form large (>500 μm) aggregates while growing in rich medium. A non-clumping variant (NCV) of 4B03 spontaneously arose in the lab, and whole-genome sequencing revealed a partial deletion in the gene encoding UDP-glucose-4-epimerase (308-324). In 27126, a knock-out of (::km) resulted in a loss of aggregation, mimicking the NCV. Microscopic analysis shows that both 4B03 and 27126 rapidly form large aggregates, whereas their respective mutants remain primarily as single planktonic cells or clusters of a few cells. Strains 4B03 and 27126 also form aggregates with chitin particles, but their mutants do not. Alcian Blue staining shows that 4B03 and 27126 produce large transparent exopolymer particles (TEP), but their mutants are deficient in this regard. This study demonstrates the capabilities of cell-cell aggregation, aggregation of chitin particles, and production of TEP in strains of , a widespread particle-associated genus of heterotrophic marine bacteria. A genetic requirement for is evident for each of the above capabilities, expanding the known breadth of requirement for this gene in biofilm-related processes.
IMPORTANCE
Heterotrophic marine bacteria have a central role in the global carbon cycle. Well-known for releasing CO2 by decomposition and respiration, they may also contribute to particulate organic matter (POM) aggregation, which can promote CO2 sequestration via the formation of marine snow. We find that two members of the prevalent particle-associated genus can form aggregates comprising cells alone or cells and chitin particles, indicating their ability to drive POM aggregation. In line with their multivalent aggregation capability, both strains produce TEP, an excreted polysaccharide central to POM aggregation in the ocean. We demonstrate a genetic requirement for in aggregation and large TEP formation, building our mechanistic understanding of these aggregative capabilities. These findings point toward a role for heterotrophic bacteria in POM aggregation in the ocean and support broader efforts to understand bacterial controls on the global carbon cycle based on microbial activities, community structure, and meta-omic profiling.
PubMed: 38958440
DOI: 10.1128/mbio.00038-24 -
Microbiology Resource Announcements Jul 2024The draft genome of a previously documented potential probiotic strain GM93m3 from raw goat milk in Nigeria is reported. The total genome size was 2,447,229 with 46...
The draft genome of a previously documented potential probiotic strain GM93m3 from raw goat milk in Nigeria is reported. The total genome size was 2,447,229 with 46 contigs and G+C content of 44.86%.
PubMed: 38958438
DOI: 10.1128/mra.00270-24 -
Turkiye Parazitolojii Dergisi Jun 2024and are enteric protozoa that can cause a variety of gastrointestinal diseases, especially in vulnerable people like children, the elderly, and those with impaired...
OBJECTIVE
and are enteric protozoa that can cause a variety of gastrointestinal diseases, especially in vulnerable people like children, the elderly, and those with impaired immune systems. In order to ascertain the microbiological quality of the recreational water from Araromi Beach in Ilaje Local Government Area, Ondo State, Nigeria. This risk assessment is of great significance to human health protection against waterborne diseases. The aim of this study was to determine the microbial quality of recreational water from Araromi Beach in Ilaje Local Government Area, Ondo State, Nigeria.
METHODS
Microscopic examination of and oocysts were done.
RESULTS
Results revealed maximum occurrence of (20 oocysts/100 mL) of water sample in the month of April and maximum occurrence of (300 cysts/100 mL) of water sample in the month of June. Additionally, according to Kolmogorov-Smirnov tests for normalcy Ho =0.05, and were not regularly distributed in the water samples collected from the beach throughout the study period. The average likelihood of contracting and infections after consuming 100 mL of beach water was 0.96 and 0.35, respectively. The risks of infection associated with was lower than those associated with in water from the beach, but were both above the acceptable risk limit of 10-4.
CONCLUSION
The results of this study indicate that and may represent serious health hazards to people who engage in aquatic activities. Adopting a comprehensive strategy that includes regular inspections, enhanced detection techniques, and the prevention of aquatic environment pollution may provide clean and safe recreational water for all, thereby safeguarding the public's health.
Topics: Cryptosporidium parvum; Giardia lamblia; Nigeria; Humans; Seawater; Risk Assessment; Water Microbiology; Giardiasis; Cryptosporidiosis; Recreation; Oocysts
PubMed: 38958402
DOI: 10.4274/tpd.galenos.2024.69733 -
Geobiology Jul 2024Lacustrine carbonates are a powerful archive of paleoenvironmental information but are susceptible to post-depositional alteration. Microbial metabolisms can drive such...
Lacustrine carbonates are a powerful archive of paleoenvironmental information but are susceptible to post-depositional alteration. Microbial metabolisms can drive such alteration by changing carbonate saturation in situ, thereby driving dissolution or precipitation. The net impact these microbial processes have on the primary δO, δC, and Δ values of lacustrine carbonate is not fully known. We studied the evolution of microbial community structure and the porewater and sediment geochemistry in the upper ~30 cm of sediment from two shoreline sites at Green Lake, Fayetteville, NY over 2 years of seasonal sampling. We linked seasonal and depth-based changes of porewater carbonate chemistry to microbial community composition, in situ carbon cycling (using δC values of carbonate, dissolved inorganic carbon (DIC), and organic matter), and dominant allochems and facies. We interpret that microbial processes are a dominant control on carbon cycling within the sediment, affecting porewater DIC, aqueous carbon chemistry, and carbonate carbon and clumped isotope geochemistry. Across all seasons and sites, microbial organic matter remineralization lowers the δC of the porewater DIC. Elevated carbonate saturation states in the sediment porewaters (Ω > 3) were attributed to microbes from groups capable of sulfate reduction, which were abundant in the sediment below 5 cm depth. The nearshore carbonate sediments at Green Lake are mainly composed of microbialite intraclasts/oncoids, charophytes, larger calcite crystals, and authigenic micrite-each with a different origin. Authigenic micrite is interpreted to have precipitated in situ from the supersaturated porewaters from microbial metabolism. The stable carbon isotope values (δC) and clumped isotope values (Δ) of bulk carbonate sediments from the same depth horizons and site varied depending on both the sampling season and the specific location within a site, indicating localized (μm to mm) controls on carbon and clumped isotope values. Our results suggest that biological processes are a dominant control on carbon chemistry within the sedimentary subsurface of the shorelines of Green Lake, from actively forming microbialites to pore space organic matter remineralization and micrite authigenesis. A combination of biological activity, hydrologic balance, and allochem composition of the sediments set the stable carbon, oxygen, and clumped isotope signals preserved by the Green Lake carbonate sediments.
Topics: Geologic Sediments; Lakes; Carbon Isotopes; Carbonates; New York; Microbiota; Carbon Cycle; Bacteria; Seasons
PubMed: 38958391
DOI: 10.1111/gbi.12609 -
Turkiye Parazitolojii Dergisi Jun 2024Recent studies determined that the amoeboid form of acts as a factor in stimulating the host's immune responses and ultimately results in urticaria and other skin...
OBJECTIVE
Recent studies determined that the amoeboid form of acts as a factor in stimulating the host's immune responses and ultimately results in urticaria and other skin disorders. The present study was conducted in order to determine the prevalence of in people referred to Bushehr city health centers and the relationship of this parasite with urticaria.
METHODS
Fecal samples were collected from 180 males and females referred to Bushehr health centers and a questionnaire containing demographic information was completed for each person. Samples were examined by preparing direct smear (wet mount) and then formalin-detergent sedimentation techniques. Data were analyzed using SPSS 22.0 software and chi-square test.
RESULTS
The results showed that 11.1% of cases infected with and 55% of patients with had various gastrointestinal symptoms. Statistical analysis showed that there was no significant relationship between infection with some demographic factors such as sex, age, literacy level and residence, but this was significant with some clinical symptoms such as itching and urticaria.
CONCLUSION
Despite the existence of conflicting information and many ambiguities about the , this emerging pathogen is very important in terms of causing allergic and skin disorders in sufferers, therefore, it is necessary that patients with urticaria be evaluated for along with other diagnostic procedures and physicians should request a test before any medical intervention. Thus, diagnosis and treatment of these people can play an important role in improving the health of society.
Topics: Humans; Female; Male; Blastocystis Infections; Adult; Prevalence; Middle Aged; Adolescent; Turkey; Feces; Urticaria; Young Adult; Blastocystis; Child; Aged; Child, Preschool; Surveys and Questionnaires
PubMed: 38958390
DOI: 10.4274/tpd.galenos.2024.44366 -
Turkiye Parazitolojii Dergisi Jun 2024is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic...
OBJECTIVE
is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic disease, but there is a need for new drugs since 1980's with increasing numbers of reported resistance. In this study, it was aimed to determine the antitrichomonal activity of the major components of (cinnamon) and (thyme) essential oils, cinnamaldehyde, carvacrol and thymol against metronidazole resistant and susceptible strains, and to determine their interaction with metronidazole by checkerboard method.
METHODS
Cinnamaldehyde, carvacrol, thymol and metronidazole were obtained commercially. Two clinical isolates and one metronidazole resistant reference strain were used in the study. MIC50 and MLC values of essential oil components and metronidazole were determined by broth microdilution method. The combinations of essential oil components with metronidazole were determined by the checkerboard method.
RESULTS
According to activity tests, cinnamaldehyde was determined to be most effective essential oil component. Clinical isolates were susceptible to metronidazole. In combination study, metronidazole showed synergy with cinnamaldehyde and carvacrol, and partial synergy with thymol.
CONCLUSION
It was determined that cinnamaldehyde, carvacrol and thymol, which are known to have high antimicrobial activity, also have strong activity against isolates and show a synergistic interaction with metronidazole. The use of metronidazole at lower doses in the synergistic interaction may contribute to the literature in terms of reducing drug side effects, creating a versatile antimicrobial target, and reducing the rate of resistance development.
Topics: Acrolein; Thymol; Cymenes; Drug Synergism; Metronidazole; Humans; Oils, Volatile; Thymus Plant; Trichomonas vaginalis; Monoterpenes; Female; Cinnamomum zeylanicum; Antiprotozoal Agents; Microbial Sensitivity Tests; Drug Resistance
PubMed: 38958374
DOI: 10.4274/tpd.galenos.2024.91855 -
Critical Care Science 2024
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Community-Acquired Infections; Fatal Outcome; Male
PubMed: 38958372
DOI: 10.62675/2965-2774.20240040-en -
Brazilian Journal of Medical and... 2024Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection...
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.
Topics: Animals; Adjuvants, Immunologic; Tuberculosis Vaccines; Mycobacterium tuberculosis; Mice; Disease Models, Animal; Female; Antigens, Bacterial; Acyltransferases; Vaccines, Subunit; Bacterial Proteins; Tuberculosis; Latent Tuberculosis; Mice, Inbred BALB C; Administration, Intranasal
PubMed: 38958367
DOI: 10.1590/1414-431X2024e13409