mSphere最新文献

{"title":"Prophages are infrequently associated with antibiotic resistance in <i>Pseudomonas aeruginosa</i> clinical isolates.","authors":"Tony H Chang, Julie D Pourtois, Naomi L Haddock, Daisuke Furukawa, Kate E Kelly, Derek F Amanatullah, Elizabeth Burgener, Carlos Milla, Niaz Banaei, Paul L Bollyky","doi":"10.1128/msphere.00904-24","DOIUrl":"10.1128/msphere.00904-24","url":null,"abstract":"<p><p>Lysogenic bacteriophages can integrate their genome into the bacterial chromosome in the form of a prophage and can promote genetic transfer between bacterial strains <i>in vitro</i>. However, the contribution of lysogenic bacteriophages to the incidence of antimicrobial resistance (AMR) in clinical settings is poorly understood. Here, in a set of 186 clinical isolates of <i>Pseudomonas aeruginosa</i> collected from respiratory cultures from 82 patients with cystic fibrosis, we evaluate the links between prophage counts and both genomic and phenotypic resistance to six anti-pseudomonal antibiotics: tobramycin, colistin, ciprofloxacin, meropenem, aztreonam, and piperacillin-tazobactam. We identified 239 different prophages in total. We find that <i>P. aeruginosa</i> isolates contain on average 3.06 ± 1.84 (SD) predicted prophages. We find no significant association between the number of prophages per isolate and the minimum inhibitory concentration for any of these antibiotics. We then investigate the relationship between particular prophages and AMR. We identify a single lysogenic phage associated with phenotypic resistance to the antibiotic tobramycin and, consistent with this association, we observe that AMR genes associated with resistance to tobramycin are more likely to be found when this prophage is present. However, we find that they are not encoded directly on prophage sequences. Additionally, we identify a single prophage statistically associated with ciprofloxacin resistance but do not identify any genes associated with ciprofloxacin phenotypic resistance. These findings suggest that prophages are only infrequently associated with the AMR genes in clinical isolates of <i>P. aeruginosa</i>.IMPORTANCEAntibiotic-resistant infections of <i>Pseudomonas aeruginosa</i> (<i>Pa</i>), a leading pathogen in patients with cystic fibrosis (CF), are a global health threat. While lysogenic bacteriophages are known to facilitate horizontal gene transfer, their role in promoting antibiotic resistance in clinical settings remains poorly understood. In our analysis of 186 clinical isolates of <i>P. aeruginosa</i> from CF patients, we find that prophage abundance does not predict phenotypic resistance to key antibiotics but that specific prophages are infrequently associated with tobramycin resistance genes. In addition, we do not find antimicrobial resistance (AMR) genes encoded directly on prophages. These results highlight that while phages can be associated with AMR, phage-mediated AMR transfer may be rare in clinical isolates and difficult to identify. This work is important for future efforts on mitigating AMR in CFCF and other vulnerable populations affected by <i>Pa</i> infections and advances our understanding of bacterial-phage dynamics in clinical infections.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0090424"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal administration of <i>Lactiplantibacillus plantarum</i> ATCC 202195 with or without fructooligosaccharide in Bangladesh: a placebo-controlled randomized trial.","authors":"Lisa G Pell, Huma Qamar, Diego G Bassani, Cole Heasley, Celine Funk, Chun-Yuan Chen, Jakaria Shawon, Karen M O'Callaghan, Eleanor Pullenayegum, Davidson H Hamer, Rashidul Haque, Mamun Kabir, Tahmeed Ahmed, Ciobha O'Kelly, Md Iqbal Hossain, Afreen Z Khan, Miranda G Loutet, Mohammad Shahidul Islam, Shaun K Morris, Prakesh S Shah, Philip M Sherman, Shamima Sultana, Abdullah Al Mahmud, Samir K Saha, Shafiqul A Sarker, Daniel E Roth","doi":"10.1128/msphere.01032-24","DOIUrl":"10.1128/msphere.01032-24","url":null,"abstract":"<p><p><i>Lactiplantibacillus plantarum</i> ATCC 202195 (LP202195) plus fructooligosaccharide (FOS) for 7 days was previously shown to colonize the infant intestine up to 6 months of age and reduced sepsis rates among young infants in rural India. In a phase 2 randomized controlled trial in Dhaka, Bangladesh (<i>N</i> = 519), neonatal administration of LP202195 for 1 or 7 days, with or without FOS, increased LP202195 stool abundance from 14 to 60 days of age, versus placebo. Abundance progressively declined in the post-administration period and did not persist beyond 2 months of age. FOS did not affect LP202195 abundance or its duration of persistence. All regimens were well-tolerated and safe. The absence of LP202195 colonization was inconsistent with results from a prior trial. Additional large-scale trials of LP202195 ± FOS are needed to establish its efficacy in infants who do not become LP202195-colonized.</p><p><strong>Importance: </strong>Among infants born in Dhaka, Bangladesh, a 7-day regimen of <i>Lactiplantibacillus plantarum</i> ATCC 202195 (LP202195) plus fructooligosaccharide (FOS) did not colonize the infant gastrointestinal (GI) tract. The absence of colonization is inconsistent with a prior study of the same synbiotic regimen in India, in which LP202195 was shown to persist in the infant GI tract for up to 6 months. Sustained LP202195 colonization was thought to be required for the probiotic to impart its beneficial impact on newborn sepsis. Therefore, additional trials are warranted to confirm the previously observed effects of LP202195 on infant clinical outcomes in the absence of LP202195 colonization. Moreover, since regimens of LP202195 that did not include FOS were indistinguishable from the synbiotic in terms of colonization, safety, and tolerability, future trials should assess the role of FOS for clinical efficacy; removing FOS would reduce costs, an important consideration for scale-up.</p><p><strong>Clinical trials: </strong>This study has been registered at ClinicalTrials.gov as NCT05180201.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0103224"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targets for the diagnosis of <i>Acanthamoeba</i> eye infections include four cyst wall proteins and the mannose-binding domain of the trophozoite mannose-binding protein.","authors":"Bharath Kanakapura Sundararaj, Manish Goyal, John Samuelson","doi":"10.1128/msphere.00948-24","DOIUrl":"10.1128/msphere.00948-24","url":null,"abstract":"<p><p><i>Acanthamoebae</i>, which are free-living amoebae, cause corneal inflammation (keratitis) and blindness, if not quickly diagnosed and effectively treated. The walls of <i>Acanthamoeba</i> cysts contain cellulose and have two layers connected by conical ostioles. Cysts are identified by <i>in vivo</i> confocal microscopy of the eye or calcofluor-white- or Giemsa-labeling of corneal scrapings, both of which demand great expertise. Trophozoites, which use a mannose-binding protein to adhere to keratinocytes, are identified in eye cultures that delay diagnosis and treatment. We recently used structural and experimental methods to characterize cellulose-binding domains of Luke and Leo lectins, which are abundant in the inner layer and ostioles. However, no antibodies have been made to these lectins or to a Jonah lectin and a laccase, which are abundant in the outer layer. Here, confocal microscopy of rabbit antibodies (rAbs) to recombinant Luke, Leo, Jonah, and laccase supported localizations of GFP-tagged proteins in walls of transfected <i>Acanthamoebae</i>. rAbs efficiently detected calcofluor white-labeled cysts of 10 of the 11 <i>Acanthamoeba</i> isolates tested, including six T4 genotypes that cause most cases of keratitis. Further, laccase shed into the medium during encystation was detected by an enzyme-linked immunoassay. Structural and experimental methods identified the mannose-binding domain (ManBD) of the <i>Acanthamoeba</i> mannose-binding protein, while rAbs to the ManBD efficiently detected DAPI-labeled trophozoites from all 11 <i>Acanthamoeba</i> isolates tested. We conclude that antibodies to four cyst wall proteins and the ManBD efficiently identify <i>Acanthamoeba</i> cysts and trophozoites, respectively.IMPORTANCEFree-living amoeba in the soil or water cause <i>Acanthamoeba</i> keratitis, which is diagnosed by identification of unlabeled cysts by <i>in vivo</i> confocal microscopy of the eye or calcofluor-white (CFW) labeled cysts by fluorescence microscopy of corneal scrapings. Alternatively, <i>Acanthamoeba</i> infections are diagnosed by the identification of trophozoites in eye cultures. Here, we showed that rabbit antibodies (rAbs) to four abundant cyst wall proteins (Jonah, Luke, Leo, and laccase) each efficiently identify CFW-labeled cysts of 10 of the 11 <i>Acanthamoeba</i> isolates tested. Further, laccase released into the medium by encysting <i>Acanthamoebae</i> was detected by an enzyme-linked immunoassay. We also showed that rAbs to the mannose-binding domain (ManBD) of the <i>Acanthamoeba</i> mannose-binding protein, which mediates adherence of trophozoites to keratinocytes, efficiently identify DAPI-labeled trophozoites of all 11 <i>Acanthamoeba</i> isolates tested. In summary, four wall proteins and the ManBD appear to be excellent targets for the diagnosis of <i>Acanthamoeba</i> cysts and trophozoites, respectively.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0094824"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relevance of oncobiome in breast cancer evolution in an Argentine cohort.","authors":"Leonardo Néstor Rubén Dandeu, Joel Lachovsky, Sofía Sidlik, Pablo Marenco, Daniela Orschanski, Pablo Aguilera, Martín Vázquez, María Del Pilar Carballo, Elmer Fernández, Alberto Penas-Steinhardt, Norma Alejandra Chasseing, Vivian Labovsky","doi":"10.1128/msphere.00597-24","DOIUrl":"10.1128/msphere.00597-24","url":null,"abstract":"<p><p>Breast cancer is the leading cause of cancer deaths in women worldwide, with about 20,000 cases annually in Argentina. While age, diet, and genetics are known risk factors, most breast cancer cases have unknown causes, necessitating the discovery of new risk factors. The aim of this study was the analysis of the prognostic relevance of the oncobiome in Argentinean breast cancer patients. Sequencing of the V4 region 16S rRNA gene was performed on 34 primary breast tumor samples, using bioinformatic and statistical analyses to identify bacteria and hypothetical pathways. Each sample presented a unique microbial profile, with <i>Proteobacteria</i> being the most abundant phylum. Tumors >2 cm showed greater alpha diversity with increased nucleotide biosynthesis. Moreover, progesterone-receptor tumors showed differences in beta diversity, being progesterone receptor-positive tumors that had the highest expression of <i>Acinetobacter</i> and <i>Moraxella</i>. In disease progression, the phylum <i>Chloroflexi</i> was prevalent in tumors of surviving patients. <i>Acinetobacter</i> and <i>Cloacibacterium</i> genera were significantly higher in patients without events and those without metastasis. We found that nucleotide and cell-structure biosynthesis, and lipid metabolism pathways were enriched in tumors with poor progression, whereas amino-acid degradation was increased in tumors of surviving patients. This finding is an indication that tumor cells are taking advantage of this effect of the microbiome during tumor progression. We conclude that oncobiome is dysbiotic in these patients, with distinct patterns in those with poor progression. Suggesting a link between the oncobiome and cancer progression, paving the way for new therapies to improve patient quality of life and survival.</p><p><strong>Importance: </strong>This is the first study to investigate the relevance of the oncobiome in the evolution of breast cancer in a cohort of Argentine patients. It also highlights the need for further research in this area to improve our understanding of the role of the microbiome in this disease and potentially identify new therapeutic targets or prognostic indicators. Understanding the complex interaction between the microbiome, the tumor microenvironment, and the pathogenesis of breast cancer holds the promise of more personalized and effective treatment approaches in the future.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0059724"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diversity of <i>Campylobacter</i> species in a rhesus macaque breeding colony.","authors":"Irving Nachamkin","doi":"10.1128/msphere.00991-24","DOIUrl":"https://doi.org/10.1128/msphere.00991-24","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0099124"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Bifidobacterium longum</i> increases serum vitamin D metabolite levels and modulates intestinal flora to alleviate osteoporosis in mice.","authors":"Hongchao Wang, Gao Tian, Zhangming Pei, Xihua Yu, Yi Wang, Fuchun Xu, Jianxin Zhao, Shourong Lu, Wenwei Lu","doi":"10.1128/msphere.01039-24","DOIUrl":"10.1128/msphere.01039-24","url":null,"abstract":"<p><p>The elderly population is prone to osteoporosis, owing to the deterioration of the skin, liver, and kidney functions. Vitamin D (VD) supplementation has a limited effect, and VD deficiency is mostly treated with medication. Several studies have shown that the gut microbiota alters intestinal VD metabolism and that probiotic supplements can influence circulating VD levels. Therefore, in the present study, we screened a strain of <i>Bifidobacterium longum</i> FSHHK13M1 that can increase the level of VD metabolites in the fermented supernatant species <i>in vitro</i> by modeling fecal bacterial fermentation. The results showed that FSHHK13M1 intervention significantly increased the serum levels of 1,25-dihydroxy VD and osteocalcin. It activated the expression of the VDR, OPG, Wnt10b/β-catenin, and Runx2/Osterix pathways and inhibited the expression of RANKL/RANK pathway. Furthermore, there was an enhancement in the quantity of bone trabeculae and the proportion of bone volume. Concurrently, the gut microbiota in mice with osteoporosis exhibited signs of imbalance. FSHHK13M1 intervention increased the relative abundance of specific bacteria, such as <i>Faecalibaculum rodentium</i>, <i>Limosilactobacillus fermentum</i>, <i>Bifidobacterium pseudolongum</i>, and <i>Akkermansia muciniphila</i>. These results suggest that <i>B. longum</i> FSHHK13M1 alleviates retinoic acid-induced osteoporosis symptoms by modulating related genes, regulating the intestinal flora and increasing the level of active VD.IMPORTANCEOsteoporosis is a systemic metabolic disease in which the patient's bone mass decreases for a variety of reasons, and the microstructure of the bone tissue is altered, leading to an increase in bone brittleness and susceptibility to fracture. Osteoporosis is almost always present in the elderly population, and fractures from falls are an important predisposing factor for mortality risk in the elderly population. Supplementation is quite limited for them as they are not able to utilize vitamin D well due to declining liver, kidney, and skin functions. In the present study, a strain of <i>Bifidobacterium longum</i> probiotic was found to increase the levels of the active form of vitamin D and ameliorate osteoporosis. This may play an important role in preventing osteoporosis and reducing fracture risk in the elderly.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0103924"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell differentiation controls iron assimilation in the choanoflagellate <i>Salpingoeca rosetta</i>.","authors":"Fredrick Leon, Jesus M Espinoza-Esparza, Vicki Deng, Maxwell C Coyle, Sarah Espinoza, David S Booth","doi":"10.1128/msphere.00917-24","DOIUrl":"10.1128/msphere.00917-24","url":null,"abstract":"<p><p>Marine microeukaryotes have evolved diverse cellular features that link their life histories to surrounding environments. How those dynamic life histories intersect with the ecological functions of microeukaryotes remains a frontier to understanding their roles in critical biogeochemical cycles. Choanoflagellates, phagotrophs that cycle nutrients through filter feeding, provide models to explore this intersection, for many choanoflagellate species transition between life history stages by differentiating into distinct cell types. Here, we report that cell differentiation in the marine choanoflagellate <i>Salpingoeca rosetta</i> endows one of its cell types with the ability to utilize insoluble ferric colloids. These colloids are a predominant form of iron in marine environments and are largely inaccessible to cell-walled microbes. Therefore, choanoflagellates and other phagotrophic eukaryotes may serve critical ecological roles by cycling this essential nutrient through iron utilization pathways. We found that <i>S. rosetta</i> can utilize these ferric colloids via the expression of a cytochrome b561 iron reductase (<i>cytb561a</i>). This gene and its mammalian ortholog, the duodenal cytochrome b561 (<i>DCYTB</i>) that reduces ferric cations for uptake in gut epithelia, belong to a subgroup of cytochrome b561 proteins with distinct biochemical features that contribute to iron reduction activity. Overall, our findings provide insight into the ecological roles choanoflagellates perform and inform reconstructions of early animal evolution where functionally distinct cell types became an integrated whole at the origin of animal multicellularity.</p><p><strong>Importance: </strong>This study examines how cell differentiation in a choanoflagellate enables the uptake of iron, an essential nutrient. Choanoflagellates are widespread, aquatic microeukaryotes that are the closest living relatives of animals. Similar to their animal relatives, we found that the model choanoflagellate, <i>S. rosetta</i>, divides metabolic functions between distinct cell types. One cell type uses an iron reductase to acquire ferric colloids, a key source of iron in the ocean. We also observed that <i>S. rosetta</i> has three variants of this reductase, each with distinct biochemical properties that likely lead to differences in how they reduce iron. These reductases are variably distributed across ocean regions, suggesting a role for choanoflagellates in cycling iron in marine environments.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0091724"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-scale CRISPR/Cas9 screening reveals the role of <i>PSMD4</i> in colibactin-mediated cell cycle arrest.","authors":"Michael W Dougherty, Ryan M Hoffmann, Maria C Hernandez, Yougant Airan, Raad Z Gharaibeh, Seth B Herzon, Ye Yang, Christian Jobin","doi":"10.1128/msphere.00692-24","DOIUrl":"10.1128/msphere.00692-24","url":null,"abstract":"<p><p>Colibactin is a genotoxic secondary metabolite produced by certain <i>Enterobacteriaceae</i> strains that populate the intestine and produces a specific mutational signature in human colonocytes. However, the host pathways involved in colibactin response remain unclear. To address this gap, we performed genome-wide CRISPR/Cas9 knockout screens and RNA sequencing utilizing live <i>pks⁺</i> bacteria and a synthetic colibactin analog. We identified 20 enriched genes with a MAGeCK score of >2.0 in both screens, including proteasomal subunits (e.g., <i>PSMG4</i> and <i>PSMD4</i>), RNA processing factors (e.g., <i>SF1</i> and <i>PRPF8</i>), and RNA polymerase III (e.g., <i>CRCP</i>), and validated the role of <i>PSMD4</i> in colibactin sensitization. <i>PSMD4</i> knockout in HEK293T and HT-29 cells promoted cell viability and ameliorated G2-M cell cycle arrest but did not affect the amount of phosphorylated H2AX foci after exposure to synthetic colibactin 742. Consistent with these observations, <i>PSMD4</i>^-/- cells had a significantly higher colony formation rate and bigger colony size than control cells after 742 exposure. These findings suggest that <i>PSMD4</i> regulates cell cycle arrest following colibactin-induced DNA damage and that cells with <i>PSMD4</i> deficiency may continue to replicate despite DNA damage, potentially increasing the risk of malignant transformation.</p><p><strong>Importance: </strong>Colibactin has been implicated as a causative agent of colorectal cancer. However, colibactin-producing bacteria are also present in many healthy individuals, leading to the hypothesis that some aspects of colibactin regulation or host response dictate the molecule's carcinogenic potential. Elucidating the host-response pathways involved in dictating cell fate after colibactin intoxication has been difficult, partially due to an inability to isolate the molecule. This study provides the first high-throughput CRISPR/Cas9 screening to identify genes conferring colibactin sensitivity. Here, we utilize both bacterial infection and a synthetic colibactin analog to identify genes directly involved in colibactin response. These findings provide insight into how differences in gene expression may render certain individuals more vulnerable to colibactin-initiated tumor formation after DNA damage.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0069224"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motility-dependent processes in <i>Toxoplasma gondii</i> tachyzoites and bradyzoites: same same but different.","authors":"Robyn S Kent, Gary E Ward","doi":"10.1128/msphere.00855-24","DOIUrl":"10.1128/msphere.00855-24","url":null,"abstract":"<p><p>During infection, <i>Toxoplasma gondii</i> tachyzoites must be able to move in order to migrate through tissues, cross biological barriers, and penetrate into and egress from cells they infect. Bradyzoite-stage parasites, which establish infection in naïve hosts, also require motility to escape from cysts after they are ingested and to subsequently migrate to the gut wall, where they either invade cells of the intestinal epithelium or squeeze between these cells to infect the underlying tissue. Little is known about the motility of bradyzoites, which we analyze in detail here and compare to the well-characterized motility and motility-dependent processes of tachyzoites. Unexpectedly, bradyzoites were found to be as motile as tachyzoites in a three-dimensional model extracellular matrix, and they showed increased invasion into and transmigration across monolayers of certain cell types, consistent with their need to establish infection in the gut. The motility of the two stages was inhibited to the same extent by cytochalasin D and KNX-002, compounds known to target the parasite's actomyosin-based motor. Other compounds that impact tachyzoite motility (tachyplegin and enhancer 5) have a reduced effect on bradyzoites. Furthermore, rapid bradyzoite egress from infected cells is not triggered by treatment with calcium ionophores, as it is with tachyzoites. The similarities and differences between these two life cycle stages highlight the need to characterize both tachyzoites and bradyzoites for a more complete understanding of the role of motility in the parasite life cycle and the effect that motility-targeting therapeutics will have on disease establishment and progression.</p><p><strong>Importance: </strong><i>Toxoplasma gondii</i> is a parasite that chronically infects around one-third of the world's population. <i>Toxoplasma</i> uses motility for multiple purposes during infection, including extracellular migration, invasion into host cells, and host cell egress. These motility-dependent processes have been extensively studied in the life cycle stage responsible for acute infection, the tachyzoite. In contrast, motility and motility-dependent processes are poorly understood in bradyzoite-stage parasites, which are responsible for both establishing infection after consumption of infected meat and initiating potentially life-threatening reactivated infections in the brains of immunocompromised individuals. We show here that the motility and motility-dependent processes of bradyzoites are similar in many respects to those of tachyzoites but markedly different in others. The results of this study highlight the need to consider both life cycle stages in attempts to develop drugs targeting parasite motility and the signaling processes that regulate motility-dependent processes during infection by these important human pathogens.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0085524"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virus-induced perturbations in the mouse microbiome are impacted by microbial experience.","authors":"Shanley N Roach, Wendy Phillips, Lauren M Pross, Autumn E Sanders, Mark J Pierson, Ryan C Hunter, Ryan A Langlois","doi":"10.1128/msphere.00563-24","DOIUrl":"10.1128/msphere.00563-24","url":null,"abstract":"<p><p>The bacterial microbiome has a major impact on health and can shape metabolism, host tolerance, immune responses, and the outcome of future infections. The bacterial microbiome is highly variable between individuals. Specific pathogen-free animals have reduced microbiome diversity, making it difficult to evaluate the impact of infection-induced microbiome disruption that would be observed in free-living animals, including people. Mice are commonly used as a preclinical model but unfortunately often fail to predict translation success or failure, particularly for immune and infectious disease-targeting therapies. Here, we utilize pet store mouse cohoused \"dirty\" mice with diverse microbial experience to explore how host variability and infection may be interacting to drive unique microbiome changes. We found that cohoused animals had significantly increased bacterial diversity in the small intestine and cecum but not in the large intestine. There were differentially abundant taxa between clean and dirty animals in all three tissues. After infection with influenza A virus, samples clustered by both housing condition and infection status in the cecum and large intestine, while small intestine samples clustered predominantly by infection. Altogether, these results highlight the differential impact of housing, infection, and interaction between the two in dictating community composition across the gastrointestinal microbiome.IMPORTANCETraditionally housed pathogen-free mouse models do not fully capture the natural variability observed among human microbiomes, which may underlie their poor translationally predictive value. Understanding the difference between pathogen-induced shifts in the bacterial microbiome and natural microbiome variance is a major hurdle to determining bacterial biomarkers of disease. It is also critical to understand how diverse baseline microbiomes may be differentially impacted by infection and contribute to disease. Pet store cohoused \"dirty\" mice have diverse microbial experiences and microbiomes, allowing us to evaluate how baseline variation, infection, and interaction between the two impact the microbiome.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0056324"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}