mSphere最新文献

{"title":"mSphere of Influence: The challenge of screening for essential protein kinases in <i>Trypanosoma cruzi</i>.","authors":"Miguel A Chiurillo","doi":"10.1128/msphere.00598-24","DOIUrl":"10.1128/msphere.00598-24","url":null,"abstract":"<p><p>Miguel Chiurillo works in the field of protein kinases, studying their role in cell signaling and cell cycle progression in <i>Trypanosoma cruzi</i>. In this mSphere of Influence article, he reflects on how the research articles \"Systematic functional analysis of <i>Leishmania</i> protein kinases identifies regulators of differentiation or survival\" by Baker et al. and \"Screening the <i>Toxoplasma</i> kinome with high throughput tagging identifies a regulator of invasion and egress\" by Smith et al. made an impact on his understanding of the complexity of the <i>Trypanosoma cruzi</i> kinome and the challenges to unravel it.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0059824"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053021","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":"Structural analysis of extracellular ATP-independent chaperones of streptococcal species and protein substrate interactions.","authors":"Charles Agbavor, Madeline Torres, Nicole L Inniss, Sarah Latimer, George Minasov, Ludmilla Shuvalova, Zdzislaw Wawrzak, Dominika Borek, Zbyszek Otwinowski, Peter J Stogios, Alexei Savchenko, Wayne F Anderson, Karla J F Satchell, Laty A Cahoon","doi":"10.1128/msphere.01078-24","DOIUrl":"10.1128/msphere.01078-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;During infection, bacterial pathogens rely on secreted virulence factors to manipulate the host cell. However, in gram-positive bacteria, the molecular mechanisms underlying the folding and activity of these virulence factors after membrane translocation are not clear. Here, we solved the protein structures of two secreted parvulin and two secreted cyclophilin-like peptidyl-prolyl isomerase (PPIase) ATP-independent chaperones found in gram-positive streptococcal species. The extracellular parvulin-type PPIase, PrsA in &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; and &lt;i&gt;Streptococcus mutans&lt;/i&gt; maintain dimeric crystal structures reminiscent of folding catalysts that consist of two domains, a PPIase and foldase domain. Structural comparison of the two cyclophilin-like extracellular chaperones from &lt;i&gt;S. pneumoniae&lt;/i&gt; and &lt;i&gt;Streptococcus pyogenes&lt;/i&gt; with other cyclophilins demonstrates that this group of cyclophilin-like chaperones has novel structural appendages formed by 9- and 24-residue insertions. Furthermore, we demonstrate that deletion of &lt;i&gt;prsA&lt;/i&gt; and &lt;i&gt;slrA&lt;/i&gt; genes impairs the secretion of the cholesterol-dependent pore-forming toxin, pneumolysin in &lt;i&gt;S. pneumoniae&lt;/i&gt;. Using protein pull-down and biophysical assays, we demonstrate a direct interaction between PrsA and SlrA with Ply. Then, we developed chaperone-assisted folding assays that show that the &lt;i&gt;S. pneumoniae&lt;/i&gt; PrsA and SlrA extracellular chaperones accelerate pneumolysin folding. In addition, we demonstrate that SlrA and, for the first time, &lt;i&gt;S. pyogene&lt;/i&gt;s PpiA exhibit PPIase activity and can bind the immunosuppressive drug, cyclosporine A. Altogether, these findings suggest a mechanistic role for streptococcal PPIase chaperones in the activity and folding of secreted virulence factors such as pneumolysin.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Streptococcal species are a leading cause of lower respiratory infections that annually affect millions of people worldwide. During infection, streptococcal species secrete a medley of virulence factors that allow the bacteria to colonize and translocate to deeper tissues. In many gram-positive bacteria, virulence factors are secreted from the cytosol across the bacterial membrane in an unfolded state. The bacterial membrane-cell wall interface is exposed to the potentially harsh extracellular environment, making it difficult for native virulence factors to fold before being released into the host. ATP-independent PPIase-type chaperones, PrsA and SlrA, are thought to facilitate folding and stabilization of several unfolded proteins to promote the colonization and spread of streptococci. Here, we present crystal structures of the molecular chaperones of PrsA and SlrA homologs from streptococcal species. We provide evidence that the &lt;i&gt;Streptococcus pyogenes&lt;/i&gt; SlrA homolog, PpiA, has PPIase activity and binds to cyclosporine A. In addition, we show that &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; PrsA and SlrA directly interact and fold the ch","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0107824"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059866","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":"First-ever ASM Global Research Symposium on Microbes in Human Health in Tsinghua, Beijing, China.","authors":"Sai Luo, Ya-Ting Wang","doi":"10.1128/msphere.01092-24","DOIUrl":"https://doi.org/10.1128/msphere.01092-24","url":null,"abstract":"<p><p>The American Society for Microbiology Global Research Symposium on Microbes in Human Health, hosted in partnership with Tsinghua University, was held in Beijing, China, on 25 to 27 September 2024. The conference provided an international forum for microbiologists from different disciplines to present and discuss new findings. The meeting covered a wide range of topics, spanning across bacteria, virus, fungi, and hosts. This report summarizes the presentations and emerging themes.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0109224"},"PeriodicalIF":3.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483717","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":"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":"https://doi.org/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":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UV-irradiated rotifers for the maintenance of gnotobiotic zebrafish larvae.","authors":"Susana Márquez Rosales, Peter I Bouchard, Emily M Olmstead, Raghuveer Parthasarathy","doi":"10.1128/msphere.00698-24","DOIUrl":"https://doi.org/10.1128/msphere.00698-24","url":null,"abstract":"<p><p>Host-associated microbial communities profoundly impact the health of humans and other animals. Zebrafish have proven to be a useful model for uncovering mechanisms of host-microbe interactions, but the difficulty of maintaining germ-free or gnotobiotic zebrafish beyond 1 week post-fertilization has limited their utility. To address this, we have developed a simple protocol using UV irradiation of rotifers, a common and nutrient-rich prey species for larval zebrafish, to reduce the bacterial load associated with the rotifers by several orders of magnitude while maintaining their motility and viability. We find that though feeding with UV-treated rotifers does not preserve the sterility of germ-free fish, it enables the maintenance of pre-existing bacterial communities. Normal feeding, in striking contrast, leads to the near-total depletion of these prior populations. We measure the abundance of single- and three-species consortia of zebrafish-commensal bacteria inoculated into initially germ-free larvae in a series of experiments extending to 8 days of feeding, or 13 days post-fertilization. We find, in fish-fed UV-treated rotifers, the persistence of bacterial populations on timescales of days, together with strong species-specific variation. In addition, re-inoculation of differently labeled strains of the same zebrafish-commensal species alongside feeding leads to colonization by the new bacteria without displacement of earlier microbes. Our method will facilitate the use of gnotobiotic zebrafish for investigations of phenomena that emerge later in animal development and for studies that probe microbiome composition fluctuations and stability over extended timescales.IMPORTANCEAll animals, including humans, are host to vast microbial communities that contribute to health and disease through mechanisms that remain largely mysterious. These microbiomes are challenging to study, spurring the use of various model organisms, including zebrafish. Zebrafish, however, are difficult to raise beyond 1 week post-fertilization under gnotobiotic conditions, in other words, germ free or with known microbial constituents, a consequence of normally feeding on live prey that brings their own, generally unknown, microbes. Therefore, we developed a simple protocol in which UV irradiation of rotifers, a widely used small-animal food for larval zebrafish, facilitates the maintenance of gnotobiotic larvae. We show that pre-existing bacterial communities in larvae are minimally affected by feeding on UV-treated rotifers, in strong contrast to feeding on untreated rotifers. We demonstrate that this feeding method allows investigations of zebrafish-associated bacterial community stability over several days, allowing investigation of previously intractable questions about microbiome stability.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0069824"},"PeriodicalIF":3.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483719","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>Toxoplasma gondii</i> PROP1 is critical for autophagy and parasite viability during chronic infection.","authors":"Pariyamon Thaprawat, Fengrong Wang, Shreya Chalasani, Tracey L Schultz, Manlio Di Cristina, Vern B Carruthers","doi":"10.1128/msphere.00829-24","DOIUrl":"https://doi.org/10.1128/msphere.00829-24","url":null,"abstract":"<p><p>Macroautophagy is an important cellular process involving lysosomal degradation of cytoplasmic components, facilitated by autophagy-related proteins. In the protozoan parasite <i>Toxoplasma gondii</i>, autophagy has been demonstrated to play a key role in adapting to stress and the persistence of chronic infection. Despite limited knowledge about the core autophagy machinery in <i>T. gondii</i>, two PROPPIN family proteins (TgPROP1 and TgPROP2) have been identified with homology to Atg18/WIPI. Prior research in acute-stage tachyzoites suggests that TgPROP2 is predominantly involved in a non-autophagic function, specifically apicoplast biogenesis, while TgPROP1 may be involved in canonical autophagy. Here, we investigated the distinct roles of TgPROP1 and TgPROP2 in chronic stage <i>T. gondii</i> bradyzoites, revealing a critical role for TgPROP1, but not TgPROP2, in bradyzoite autophagy. Conditional knockdown of TgPROP2 did not impair bradyzoite autophagy. In contrast, TgPROP1 KO parasites had impaired autolysosome formation, reduced cyst burdens in chronically infected mice, and decreased viability. Together, our findings clarify the indispensable role of TgPROP1 to <i>T. gondii</i> autophagy and chronic infection.</p><p><strong>Importance: </strong>It is estimated that up to a third of the human population is chronically infected with <i>Toxoplasma gondii</i>; however, little is known about how this parasite persists long term within its hosts. Autophagy is a self-eating pathway that has recently been shown to play a key role in parasite persistence, yet few proteins that carry out this process during <i>T. gondii</i> chronic infection are known. Here, we provide evidence for a non-redundant role of TgPROP1, a protein important in the early steps of the autophagy pathway. Genetic disruption of TgPROP1 resulted in impaired autophagy and chronic infection of mice. Our results reveal a critical role for TgPROP1 in autophagy and underscore the importance of this pathway in parasite persistence.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0082924"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468574","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":"A new bacteriophage infecting <i>Staphylococcus epidermidis</i> with potential for removing biofilms by combination with chimeric lysin CHAPSH3b and vancomycin.","authors":"Ana Catarina Duarte, Lucía Fernández, Ana Rodríguez, Pilar García","doi":"10.1128/msphere.01014-24","DOIUrl":"https://doi.org/10.1128/msphere.01014-24","url":null,"abstract":"<p><p><i>Staphylococcus epidermidis</i> is the cause of serious skin and prosthetic joint infections despite being a common inhabitant of human body surfaces. However, both the rise in antibiotic resistance in this species and its ability to form biofilms are increasingly limiting the available therapeutic options against these illnesses. In this landscape, phage therapy stands out as an interesting alternative to antibiotics. In the present study, we report the isolation and characterization of a novel virulent phage infecting <i>S. epidermidis</i> (<i>Staphylococcus</i> phage IPLA-AICAT), which belongs to the <i>Herelleviridae</i> family. The estimated genome size of this virus is 139,941 bp, and sequence analysis demonstrated the absence of antibiotic resistance genes and virulence factors. This phage infects a high proportion (79%) of clinically relevant <i>S. epidermidis</i> strains and exhibits antibiofilm activity. Moreover, a combination of this phage with other antimicrobials, i.e., vancomycin and the lytic protein CHAPSH3b, further improved the reduction in surface-attached bacteria. Notably, the combination of <i>Staphylococcus</i> phage IPLA-AICAT (10⁹ PFU/mL) and CHAPSH3b (8 µM), originally designed to target <i>Staphylococcus aureus</i>, was able to reduce the number of viable cells by 3.06 log units in 5-h-old biofilms. In 24-h-old biofilms, the reduction was also significant after 6 h of treatment (2.06 log units) and 24 h of treatment (2.52 log units). These results confirm our previous data regarding the potential of phage-lysin mixtures against staphylococcal biofilms.IMPORTANCE<i>Staphylococcus epidermidis</i> is one of the main causes to device-associated infections mostly due to its ability to form stable biofilms attached to human tissues. Besides the inherent antimicrobial tolerance of biofilms, this microorganism is also increasingly becoming resistant to standard-of-care antibiotics. To fight against this problem, phage therapy is a viable option to complement the available antibiotics in the treatment of recalcitrant infections. This work describes a new phage infecting <i>S. epidermidis</i> clinical strains that is a member of the <i>Herelleviridae</i> family and the combination with other antimicrobials to further improve the reduction of biofilms. Together with the significant progress achieved in the development of diagnostic tools, phages and their derived proteins will bring us much closer to a therapeutic landscape in which we are not so heavily reliant on antibiotics to combat bacterial pathogens.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0101424"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468579","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":"mSphere of Influence: Fungal behavior as a framework for the evolution of emergent traits.","authors":"Andrew J M Swafford","doi":"10.1128/msphere.00651-24","DOIUrl":"https://doi.org/10.1128/msphere.00651-24","url":null,"abstract":"<p><p>Andrew Swafford works in the field of evolutionary cell biology. In this mSphere of Influence article, he reflects on how the simultaneous introduction to the evolution of vision, the sensory biology of chytrid fungi, and a classic paper by Vrba and Gould helped shape his thinking about sensory evolution.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0065124"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468602","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":"https://doi.org/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":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-laboratory replication of pseudomyxoma peritonei tumor microbiome reveals reproducible microbial signatures.","authors":"Victoria F Nieciecki, Faith C Blum, Ryan C Johnson, Traci L Testerman, Tom J McAvoy, Mary Caitlin King, Vadim Gushchin, Jeannette M Whitmire, Kenneth G Frey, Lindsay Glang, Dessiree Peña-Gomez, Kimberly A Bishop-Lilly, Armando Sardi, D Scott Merrell, Jessica L Metcalf","doi":"10.1128/msphere.00652-24","DOIUrl":"https://doi.org/10.1128/msphere.00652-24","url":null,"abstract":"<p><p>Recent work has demonstrated that cancer-specific microbial communities often colonize tumor tissues. However, untangling low-biomass signals from environmental contamination makes this research technically challenging. We utilize pseudomyxoma peritonei (PMP), a cancer characterized by the spread of mucus-secreting cells throughout the peritoneal cavity, to develop a robust workflow for identifying reproducible tumor microbiomes. Typically originating from the rupture of an appendiceal tumor into the peritoneal cavity, metastasized tumors have been previously shown to harbor a core set of microbes. However, that work did not control for the potential contamination of these low microbial biomass samples. We expand upon these prior findings by characterizing the microbiome of 70 additional PMP tumors and six normal peritoneal control tissues along with appropriate laboratory controls. Additionally, DNA from a subset of 25 tissues was extracted and sequenced at an independent laboratory. We found evidence of reproducible microbial signatures between the replicates of six different PMP tumors that include a set of core taxa that may be introduced from surgical contamination, as well as patient-specific taxa that are also commonly implicated in colorectal cancer. In addition, preoperative chemotherapy treatment was found to reduce tumor microbiome diversity. Our findings demonstrate how independent sample replication can be a powerful approach to investigate low-biomass microbial communities associated with tumor tissues that will improve low microbial biomass research.IMPORTANCERecent work has demonstrated that microbial communities colonize over 30 different types of tumor tissues. The origin of these communities and their possible involvement in carcinogenesis or cancer treatment outcomes remains an unclear, yet important area of research. A current major challenge in characterizing low-biomass, tumor-associated microbiomes is the introduction of environmental contamination during collection, handling, DNA extraction, PCR, and sequencing. Here, we provide a framework for replicating low-biomass tumor microbiome samples to help identify tumors with robust microbial signals and low background contamination. Using this replication approach, we show that pseudomyxoma peritonei (PMP) tumors host reproducible microbial communities, including organisms that have previously been associated with colorectal cancer. Incorporating sample replication into future tumor microbiome studies is a promising approach that will help identify robust signals and increase reproducibility in the field.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0065224"},"PeriodicalIF":3.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458622","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}