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518100.9768Differential Expression of fimH, ihf, upaB, and upaH Genes in Biofilms- and Suspension-Grown Bacteria From Samples of Different Uropathogenic Strains of Escherichia coli. Uropathogenic Escherichia coli (UPEC) strains are the main bacteria that cause urinary tract infections (UTIs). UPEC are a significant public health hazard due to their high proliferation, antibiotic resistance, and infection recurrence. The ability to form biofilms is a mechanism of antibiotic resistance, which requires the expression of different genes such as fimH, ihf, upaB, and upaH. Despite the relevance of biofilm formation in bacterial pathogenicity, differences in the expression level of these genes among bacterial growth conditions have been little studied. Here, we have characterized the expression of fimH, ihf, upaB, and upaH genes in biofilms and suspension-grown bacteria of different E. coli strains. These included the UPEC CFT073, the multidrug-resistant strain CDC-AR-0346, and clinical isolates obtained from UTI patients. The expression of fimH, ihf, upaB, and upaH was markedly heterogeneous in clinical isolates, both in terms of transcript levels and response to suspension or biofilm conditions. That expression pattern was distinct from the one in UPEC CFT073, where upaB and upaH were upregulated and ihf and fimH were slightly downregulated in biofilm. In conclusion, the data presented here show that the pattern of biofilm-associated genes in the clinical isolates from UTI patients is not fully related to the reference strain of UPEC CFT073. However, analysis of a larger number of samples is required.202439703715
616310.9758Microbiome responses during virulence adaptation by a phloem-feeding insect to resistant near-isogenic rice lines. The microbiomes of phloem-feeding insects include functional bacteria and yeasts essential for herbivore survival and development. Changes in microbiome composition are implicated in virulence adaptation by herbivores to host plant species or host populations (including crop varieties). We examined patterns in adaptation by the green leafhopper, Nephotettix virescens, to near-isogenic rice lines (NILs) with one or two resistance genes and the recurrent parent T65, without resistance genes. Only the line with two resistance genes was effective in reducing leafhopper fitness. After 20 generations on the resistant line, selected leafhoppers attained similar survival, weight gain, and egg laying to leafhoppers that were continually reared on the susceptible recurrent parent, indicating that they had adapted to the resistant host. By sequencing the 16s rRNA gene, we described the microbiome of leafhoppers from colonies associated with five collection sites, and continually reared or switched between NILs. The microbiomes included 69-119 OTUs of which 44 occurred in ≥90% of samples. Of these, 14 OTUs were assigned to the obligate symbiont Candidatus sulcia clade. After 20 generations of selection, collection site had a greater effect than host plant on microbiome composition. Six bacteria genera, including C. sulcia, were associated with leafhopper virulence. However, there was significant within-treatment, site-related variability in the prevalence of these taxa such that the mechanisms underlying their association with virulence remain to be determined. Our results imply that these taxa are associated with leafhopper nutrition. Ours is the first study to describe microbiome diversity and composition in rice leafhoppers. We discuss our results in light of the multiple functions of herbivore microbiomes during virulence adaptation in insect herbivores.201931695897
818720.9758Racial disparities in metastatic colorectal cancer outcomes revealed by tumor microbiome and transcriptome analysis with bevacizumab treatment. Background: Metastatic colorectal cancer (mCRC) is a heterogeneous disease, often associated with poor outcomes and resistance to therapies. The racial variations in the molecular and microbiological profiles of mCRC patients, however, remain under-explored. Methods: Using RNA-SEQ data, we extracted and analyzed actively transcribing microbiota within the tumor milieu, ensuring that the identified bacteria were not merely transient inhabitants but engaged in the tumor ecosystem. Also, we independently acquired samples from 12 mCRC patients, specifically, 6 White individuals and 6 of Black or African American descent. These samples underwent 16S rRNA sequencing. Results: Our study revealed notable racial disparities in the molecular signatures and microbiota profiles of mCRC patients. The intersection of these data showcased the potential modulating effects of specific bacteria on gene expression. Particularly, the bacteria Helicobacter cinaedi and Sphingobium herbicidovorans emerged as significant influencers, with strong correlations to the genes SELENBP1 and SNORA38, respectively. Discussion: These findings underscore the intricate interplay between host genomics and actively transcribing tumor microbiota in mCRC's pathogenesis. The identified correlations between specific bacteria and genes highlight potential avenues for targeted therapies and a more personalized therapeutic approach.202338357363
829130.9757Pseudomonas Can Survive Tailocin Killing via Persistence-Like and Heterogenous Resistance Mechanisms. Phage tail-like bacteriocins (tailocins) are bacterially produced protein toxins that mediate competitive interactions between cocolonizing bacteria. Both theoretical and experimental research has shown there are intransitive interactions between bacteriocin-producing, bacteriocin-sensitive, and bacteriocin-resistant populations, whereby producers outcompete sensitive cells, sensitive cells outcompete resistant cells, and resistant cells outcompete producers. These so-called rock-paper-scissors dynamics explain how all three populations occupy the same environment, without one driving the others extinct. Using Pseudomonas syringae as a model, we demonstrate that otherwise sensitive cells survive bacteriocin exposure through a physiological mechanism. This mechanism allows cells to survive bacteriocin killing without acquiring resistance. We show that a significant fraction of the target cells that survive a lethal dose of tailocin did not exhibit any detectable increase in survival during a subsequent exposure. Tailocin persister cells were more prevalent in stationary- rather than log-phase cultures. Of the fraction of cells that gained detectable resistance, there was a range from complete (insensitive) to incomplete (partially sensitive) resistance. By using genomic sequencing and genetic engineering, we showed that a mutation in a hypothetical gene containing 8 to 10 transmembrane domains causes tailocin high persistence and that genes of various glycosyltransferases cause incomplete and complete tailocin resistance. Importantly, of the several classes of mutations, only those causing complete tailocin resistance compromised host fitness. This result indicates that bacteria likely utilize persistence to survive bacteriocin-mediated killing without suffering the costs associated with resistance. This research provides important insight into how bacteria can escape the trap of fitness trade-offs associated with gaining de novo tailocin resistance.IMPORTANCE Bacteriocins are bacterially produced protein toxins that are proposed as antibiotic alternatives. However, a deeper understanding of the responses of target bacteria to bacteriocin exposure is lacking. Here, we show that target cells of Pseudomonas syringae survive lethal bacteriocin exposure through both physiological persistence and genetic resistance mechanisms. Cells that are not growing rapidly rely primarily on persistence, whereas those growing rapidly are more likely to survive via resistance. We identified various mutations in lipopolysaccharide biogenesis-related regions involved in tailocin persistence and resistance. By assessing host fitness of various classes of mutants, we showed that persistence and subtle resistance are mechanisms P. syringae uses to survive competition and preserve host fitness. These results have important implications for developing bacteriocins as alternative therapeutic agents.202032312747
867240.9756Pangenomic and functional investigations for dormancy and biodegradation features of an organic pollutant-degrading bacterium Rhodococcus biphenylivorans TG9. Environmental bacteria contain a wealth of untapped potential in the form of biodegradative genes. Leveraging this potential can often be confounded by a lack of understanding of fundamental survival strategies, like dormancy, for environmental stress. Investigating bacterial dormancy-to-degradation relationships enables improvement of bioremediation. Here, we couple genomic and functional assessment to provide context for key attributes of the organic pollutant-degrading strain Rhodococcus biphenylivorans TG9. Whole genome sequencing, pangenome analysis and functional characterization were performed to elucidate important genes and gene products, including antimicrobial resistance, dormancy, and degradation. Rhodococcus as a genus has strong potential for degradation and dormancy, which we demonstrate using R. biphenylivorans TG9 as a model. We identified four Resuscitation-promoting factor (Rpf) encoding genes in TG9 involved in dormancy and resuscitation. We demonstrate that R. biphenylivorans TG9 grows on fourteen typical organic pollutants, and exhibits a robust ability to degrade biphenyl and several congeners of polychlorinated biphenyls. We further induced TG9 into a dormant state and demonstrated pronounced differences in morphology and activity. Together, these results expand our understanding of the genus Rhodococcus and the relationship between dormancy and biodegradation in the presence of environmental stressors.202234688761
841850.9755The megaplasmid pCER270 of Bacillus cereus emetic strain affects the timing of the sporulation process, spore resistance properties, and germination. The Bacillus cereus group includes closely related spore-forming Gram-positive bacteria. In this group, plasmids play a crucial role in species differentiation and are essential for pathogenesis and adaptation to ecological niches. The B. cereus emetic strains are characterized by the presence of the pCER270 megaplasmid, which encodes the non-ribosomal peptide synthetase for the production of cereulide, the emetic toxin. This plasmid carries several genes that may be involved in the sporulation process. Furthermore, a transcriptomic analysis has revealed that pCER270 influences the expression of chromosome genes, particularly under sporulation conditions. In this study, we investigated the role of pCER270 on spore properties in different species of the B. cereus group. We showed that pCER270 plays a role in spore wet heat resistance and germination, with varying degrees of impact depending on the genetic background. In addition, pCER270 ensures that sporulation occurs at the appropriate time by delaying the expression of sporulation genes. This regulation of sporulation timing is controlled by the pCER270-borne Rap-Phr system, which likely regulates the phosphorylation state of Spo0A. Acquisition of the pCER270 plasmid by new strains could give them an advantage in adapting to new environments and lead to the emergence of new pathogenic strains. IMPORTANCE: The acquisition of new mobile genetic elements, such as plasmids, is essential for the pathogenesis and adaptation of bacteria belonging to the Bacillus cereus group. This can confer new phenotypic traits and beneficial functions that enable bacteria to adapt to changing environments and colonize new ecological niches. Emetic B. cereus strains cause food poisoning linked to the production of cereulide, the emetic toxin whose synthesis is due to the presence of plasmid pCER270. In the environment, cereulide provides a competitive advantage in producing bacteria against various competitors or predators. This study demonstrates that pCER270 also regulates the sporulation process, resulting in spores with improved heat resistance and germination capacity. The transfer of plasmid pCER270 among different strains of the B. cereus group may enhance their adaptation to new environments. This raises the question of the emergence of new pathogenic strains, which could pose a serious threat to human health.202439158315
516760.9754Decreased Antimicrobial Resistance Gene Richness Following Fecal Microbiota, Live-jslm (REBYOTA®) Administration: Post Hoc Analysis of PUNCH CD3. BACKGROUND: The human gastrointestinal microbiome helps maintain vital functions related to overall health, including resistance to pathogen colonization. Disruption of the microbiome, leading to loss of colonization resistance, can be caused by multiple factors, including antimicrobial use. The loss of colonization resistance may lead to establishment or proliferation of opportunistic bacteria that carry genes associated with antimicrobial resistance, potentially increasing the risk of infection by such antimicrobial-resistant bacteria. A potential approach to mitigating this risk involves restoration of healthier microbiota and pathogen colonization resistance. METHODS: A metagenomic sequencing method was used to conduct a post hoc analysis of antibiotic resistance gene richness among fecal samples from participants administered fecal microbiota, live-jslm (REBYOTA; abbreviated as RBL) or placebo in the PUNCH CD3 study (NCT03244644) for the prevention of recurrent Clostridioides difficile infection. RESULTS: At baseline, participants had higher antibiotic resistance gene richness than a representative healthy cohort. Over time, RBL responders had lower antibiotic resistance gene richness at the class, group, and mechanism levels as compared with placebo responders. These differences were evident as early as 1 week after administration and sustained for at least 6 months. RBL responders also had decreased richness of antibiotic resistance genes deemed high risk based on designated bacterial public health threats. CONCLUSIONS: These data support a model in which microbiota-based products, including RBL, may reduce antibiotic resistance gene richness, thereby possibly reducing the risk of antimicrobial-resistant organism infection. TRIAL REGISTRATION: NCT03244644 (https://clinicaltrials.gov/study/NCT03244644; 9 August 2017).202540672762
936470.9752Predictable properties of fitness landscapes induced by adaptational tradeoffs. Fitness effects of mutations depend on environmental parameters. For example, mutations that increase fitness of bacteria at high antibiotic concentration often decrease fitness in the absence of antibiotic, exemplifying a tradeoff between adaptation to environmental extremes. We develop a mathematical model for fitness landscapes generated by such tradeoffs, based on experiments that determine the antibiotic dose-response curves of Escherichia coli strains, and previous observations on antibiotic resistance mutations. Our model generates a succession of landscapes with predictable properties as antibiotic concentration is varied. The landscape is nearly smooth at low and high concentrations, but the tradeoff induces a high ruggedness at intermediate antibiotic concentrations. Despite this high ruggedness, however, all the fitness maxima in the landscapes are evolutionarily accessible from the wild type. This implies that selection for antibiotic resistance in multiple mutational steps is relatively facile despite the complexity of the underlying landscape.202032423531
843880.9752Virulence of Bacteria Colonizing Vascular Bundles in Ischemic Lower Limbs. BACKGROUND: We documented previously the presence of bacterial flora in vascular bundles, lymphatics, and lymph nodes of ischemic lower limbs amputated because of multifocal atheromatic changes that made them unsuitable for reconstructive surgery and discussed their potential role in tissue destruction. The question arose why bacterial strains inhabiting lower limb skin and considered to be saprophytes become pathogenic once they colonize deep tissues. Bacterial pathogenicity is evoked by activation of multiple virulence factors encoded by groups of genes. METHODS: We identified virulence genes in bacteria cultured from deep tissue of ischemic legs of 50 patients using a polymerase chain reaction technique. RESULTS: The staphylococcal virulence genes fnbA (fibronectin-binding protein A), cna (collagen adhesin precursor), and ica (intercellular adhesion) were present in bacteria isolated from both arteries and, to a lesser extent, skin. The IS256 gene, whose product is responsible for biofilm formation, was more frequent in bacteria retrieved from the arteries than skin bacteria. Among the virulence genes of Staphylococcus epidermidis encoding autolysin atlE, icaAB (intercellular adhesion), and biofilm insert IS256, only the latter was detected in arterial specimens. Bacteria cultured from the lymphatics did not reveal expression of eta and IS256 in arteries. The Enterococcus faecalis asa 373 (aggregation substance) and cylA (cytolysin activator) frequency was greater in arteries than in skin bacteria, as were the E. faecium cyl A genes. All Pseudomonas aeruginosa virulence genes were present in bacteria cultured from both the skin and arteries. Staphylococci colonizing arterial bundles and transported to tissues via ischemic limb lymphatics expressed virulence genes at greater frequency than did those dwelling on the skin surface. Moreover, enterococci and Pseudomonas isolated from arterial bundles expressed many virulence genes. CONCLUSIONS: These findings may add to the understanding of the mechanism of development of destructive changes in lower limb ischemic tissues by the patient's, but not hospital-acquired, bacteria, as well as the generally unsatisfactory results of antibiotic administration in these cases. More aggressive antibiotic therapy targeted at the virulent species should be applied.201626431369
880590.9751Transcriptional response of selected genes of Salmonella enterica serovar Typhimurium biofilm cells during inactivation by superheated steam. Superheated steam (SHS), produced by the addition of heat to saturated steam (SS) at the same pressure, has great advantages over conventional heat sterilization due to its high temperature and accelerated drying rate. We previously demonstrated that treatment with SHS at 200°C for 10 sec inactivated Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes biofilm cells on the surface of stainless steel to below the detection limit. However, bacteria withstanding heat stress become more resistant to other stress conditions, and may be more virulent when consumed by a host. Herein, we studied the transcriptional regulation of genes important for stress resistance and virulence in Salmonella biofilms after SHS treatments. Genes encoding heat shock proteins and general stress resistance proteins showed transcriptional surges after 1 sec of SHS treatment at 200°C, with parallel induction of stress-related regulator genes including rpoE, rpoS, and rpoH. Interestingly, Salmonella biofilm cells exposed to SHS showed decreased transcription of flagella and Salmonella pathogenicity island-1 (SPI-1) genes required for motility and invasion of host cells, respectively, whereas increased transcription of SPI-2 genes, important for bacterial survival and replication inside host cells, was detected. When the transcriptional response was compared between cells treated with SHS (200°C) and SS (100°C), SHS caused immediate changes in gene expression by shorter treatments. Understanding the status of Salmonella virulence and stress resistance induced by SHS treatments is important for wider application of SHS in controlling Salmonella biofilm formation during food production.201525440555
8188100.9751Biofilm in implant infections: its production and regulation. A significant proportion of medical implants become the focus of a device-related infection, difficult to eradicate because bacteria that cause these infections live in well-developed biofilms. Biofilm is a microbial derived sessile community characterized by cells that are irreversibly attached to a substratum or interface to each other, embedded in a matrix of extracellular polymeric substances that they have produced. Bacterial adherence and biofilm production proceed in two steps: first, an attachment to a surface and, second, a cell-to-cell adhesion, with pluristratification of bacteria onto the artificial surface. The first step requires the mediation of bacterial surface proteins, the cardinal of which is similar to S. aureus autolysin and is denominated AtlE. In staphylococci the matrix of extracellular polymeric substances of biofilm is a polymer of beta-1,6-linked N-acetylglucosamine (PIA), whose synthesis is mediated by the ica operon. Biofilm formation is partially controlled by quorum sensing, an interbacterial communication mechanism dependent on population density. The principal implants that can be compromised by biofilm associated infections are: central venous catheters, heart valves, ventricular assist devices, coronary stents, neurosurgical ventricular shunts, implantable neurological stimulators, arthro-prostheses, fracture-fixation devices, inflatable penile implants, breast implants, cochlear implants, intraocular lenses, dental implants. Biofilms play an important role in the spread of antibiotic resistance. Within the high dense bacterial population, efficient horizontal transfer of resistance and virulence genes takes place. In the future, treatments that inhibit the transcription of biofilm controlling genes might be a successful strategy in inhibiting these infections.A significant proportion of medical implants become the focus of a device-related infection, difficult to eradicate because bacteria that cause these infections live in well-developed biofilms. Biofilm is a microbial derived sessile community characterized by cells that are irreversibly attached to a substratum or interface to each other, embedded in a matrix of extracellular polymeric substances that they have produced. Bacterial adherence and biofilm production proceed in two steps: first, an attachment to a surface and, second, a cell-to-cell adhesion, with pluristratification of bacteria onto the artificial surface. The first step requires the mediation of bacterial surface proteins, the cardinal of which is similar to S. aureus autolysin and is denominated AtlE. In staphylococci the matrix of extracellular polymeric substances of biofilm is a polymer of beta-1,6-linked N-acetylglucosamine (PIA), whose synthesis is mediated by the ica operon. Biofilm formation is partially controlled by quorum sensing, an interbacterial communication mechanism dependent on population density. The principal implants that can be compromised by biofilm associated infections are: central venous catheters, heart valves, ventricular assist devices, coronary stents, neurosurgical ventricular shunts, implantable neurological stimulators, arthro-prostheses, fracture-fixation devices, inflatable penile implants, breast implants, cochlear implants, intra-ocular lenses, dental implants. Biofilms play an important role in the spread of antibiotic resistance. Within the high dense bacterial population, efficient horizontal transfer of resistance and virulence genes takes place. In the future, treatments that inhibit the transcription of biofilm controlling genes might be a successful strategy in inhibiting these infections.200516353112
106110.9751Genomic evidence of the illumination response mechanism and evolutionary history of magnetotactic bacteria within the Rhodospirillaceae family. BACKGROUND: Magnetotactic bacteria (MTB) are ubiquitous in natural aquatic environments. MTB can produce intracellular magnetic particles, navigate along geomagnetic field, and respond to light. However, the potential mechanism by which MTB respond to illumination and their evolutionary relationship with photosynthetic bacteria remain elusive. RESULTS: We utilized genomes of the well-sequenced genus Magnetospirillum, including the newly sequenced MTB strain Magnetospirillum sp. XM-1 to perform a comprehensive genomic comparison with phototrophic bacteria within the family Rhodospirillaceae regarding the illumination response mechanism. First, photoreceptor genes were identified in the genomes of both MTB and phototrophic bacteria in the Rhodospirillaceae family, but no photosynthesis genes were found in the MTB genomes. Most of the photoreceptor genes in the MTB genomes from this family encode phytochrome-domain photoreceptors that likely induce red/far-red light phototaxis. Second, illumination also causes damage within the cell, and in Rhodospirillaceae, both MTB and phototrophic bacteria possess complex but similar sets of response and repair genes, such as oxidative stress response, iron homeostasis and DNA repair system genes. Lastly, phylogenomic analysis showed that MTB cluster closely with phototrophic bacteria in this family. One photoheterotrophic genus, Phaeospirillum, clustered within and displays high genomic similarity with Magnetospirillum. Moreover, the phylogenetic tree topologies of magnetosome synthesis genes in MTB and photosynthesis genes in phototrophic bacteria from the Rhodospirillaceae family were reasonably congruent with the phylogenomic tree, suggesting that these two traits were most likely vertically transferred during the evolution of their lineages. CONCLUSION: Our new genomic data indicate that MTB and phototrophic bacteria within the family Rhodospirillaceae possess diversified photoreceptors that may be responsible for phototaxis. Their genomes also contain comprehensive stress response genes to mediate the negative effects caused by illumination. Based on phylogenetic studies, most of MTB and phototrophic bacteria in the Rhodospirillaceae family evolved vertically with magnetosome synthesis and photosynthesis genes. The ancestor of Rhodospirillaceae was likely a magnetotactic phototrophic bacteria, however, gain or loss of magnetotaxis and phototrophic abilities might have occurred during the evolution of ancestral Rhodospirillaceae lineages.201931117953
8429120.9750Comparative genomics of Thermus thermophilus and Deinococcus radiodurans: divergent routes of adaptation to thermophily and radiation resistance. BACKGROUND: Thermus thermophilus and Deinococcus radiodurans belong to a distinct bacterial clade but have remarkably different phenotypes. T. thermophilus is a thermophile, which is relatively sensitive to ionizing radiation and desiccation, whereas D. radiodurans is a mesophile, which is highly radiation- and desiccation-resistant. Here we present an in-depth comparison of the genomes of these two related but differently adapted bacteria. RESULTS: By reconstructing the evolution of Thermus and Deinococcus after the divergence from their common ancestor, we demonstrate a high level of post-divergence gene flux in both lineages. Various aspects of the adaptation to high temperature in Thermus can be attributed to horizontal gene transfer from archaea and thermophilic bacteria; many of the horizontally transferred genes are located on the single megaplasmid of Thermus. In addition, the Thermus lineage has lost a set of genes that are still present in Deinococcus and many other mesophilic bacteria but are not common among thermophiles. By contrast, Deinococcus seems to have acquired numerous genes related to stress response systems from various bacteria. A comparison of the distribution of orthologous genes among the four partitions of the Deinococcus genome and the two partitions of the Thermus genome reveals homology between the Thermus megaplasmid (pTT27) and Deinococcus megaplasmid (DR177). CONCLUSION: After the radiation from their common ancestor, the Thermus and Deinococcus lineages have taken divergent paths toward their distinct lifestyles. In addition to extensive gene loss, Thermus seems to have acquired numerous genes from thermophiles, which likely was the decisive contribution to its thermophilic adaptation. By contrast, Deinococcus lost few genes but seems to have acquired many bacterial genes that apparently enhanced its ability to survive different kinds of environmental stresses. Notwithstanding the accumulation of horizontally transferred genes, we also show that the single megaplasmid of Thermus and the DR177 megaplasmid of Deinococcus are homologous and probably were inherited from the common ancestor of these bacteria.200516242020
8430130.9750Deinococcus geothermalis: the pool of extreme radiation resistance genes shrinks. Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to resistance; and strengthen the case for a role in survival of systems involved in manganese and iron homeostasis.200717895995
6161140.9750Unraveling radiation resistance strategies in two bacterial strains from the high background radiation area of Chavara-Neendakara: A comprehensive whole genome analysis. This paper reports the results of gamma irradiation experiments and whole genome sequencing (WGS) performed on vegetative cells of two radiation resistant bacterial strains, Metabacillus halosaccharovorans (VITHBRA001) and Bacillus paralicheniformis (VITHBRA024) (D10 values 2.32 kGy and 1.42 kGy, respectively), inhabiting the top-ranking high background radiation area (HBRA) of Chavara-Neendakara placer deposit (Kerala, India). The present investigation has been carried out in the context that information on strategies of bacteria having mid-range resistance for gamma radiation is inadequate. WGS, annotation, COG and KEGG analyses and manual curation of genes helped us address the possible pathways involved in the major domains of radiation resistance, involving recombination repair, base excision repair, nucleotide excision repair and mismatch repair, and the antioxidant genes, which the candidate could activate to survive under ionizing radiation. Additionally, with the help of these data, we could compare the candidate strains with that of the extremely radiation resistant model bacterium Deinococccus radiodurans, so as to find the commonalities existing in their strategies of resistance on the one hand, and also the rationale behind the difference in D10, on the other. Genomic analysis of VITHBRA001 and VITHBRA024 has further helped us ascertain the difference in capability of radiation resistance between the two strains. Significantly, the genes such as uvsE (NER), frnE (protein protection), ppk1 and ppx (non-enzymatic metabolite production) and those for carotenoid biosynthesis, are endogenous to VITHBRA001, but absent in VITHBRA024, which could explain the former's better radiation resistance. Further, this is the first-time study performed on any bacterial population inhabiting an HBRA. This study also brings forward the two species whose radiation resistance has not been reported thus far, and add to the knowledge on radiation resistant capabilities of the phylum Firmicutes which are abundantly observed in extreme environment.202438857267
9603150.9749Resistance signatures manifested in early drug response across cancer types and species. Aim: Growing evidence points to non-genetic mechanisms underlying long-term resistance to cancer therapies. These mechanisms involve pre-existing or therapy-induced transcriptional cell states that confer resistance. However, the relationship between early transcriptional responses to treatment and the eventual emergence of resistant states remains poorly understood. Furthermore, it is unclear whether such early resistance-associated transcriptional responses are evolutionarily conserved. In this study, we examine the similarity between early transcriptional responses and long-term resistant states, assess their clinical relevance, and explore their evolutionary conservation across species. Methods: We integrated datasets on early drug responses and long-term resistance from multiple cancer cell lines, bacteria, and yeast to identify early transcriptional changes predictive of long-term resistance and assess their evolutionary conservation. Using genome-wide CRISPR-Cas9 knockout screens, we evaluated the impact of genes associated with resistant transcriptional states on drug sensitivity. Clinical datasets were analyzed to explore the prognostic value of the identified resistance-associated gene signatures. Results: We found that transcriptional states observed in drug-naive cells and shortly after treatment overlapped with those seen in fully resistant populations. Some of these shared features appear to be evolutionarily conserved. Knockout of genes marking resistant states sensitized ovarian cancer cells to Prexasertib. Moreover, early resistance gene signatures effectively distinguished therapy responders from non-responders in multiple clinical cancer trials and differentiated premalignant breast lesions that progressed to malignancy from those that remained benign. Conclusion: Early cellular transcriptional responses to therapy exhibit key similarities to fully resistant states across different drugs, cancer types, and species. Gene signatures defining these early resistance states have prognostic value in clinical settings.202541019980
8934160.9749A tradeoff between bacteriophage resistance and bacterial motility is mediated by the Rcs phosphorelay in Escherichia coli. Across the tree of life, pleiotropy is thought to constrain adaptation through evolutionary tradeoffs. However, few examples of pleiotropy exist that are well explained at the genetic level, especially for pleiotropy that is mediated by multiple genes. Here, we describe a set of pleiotropic mutations that mediate two key fitness components in bacteria: parasite resistance and motility. We subjected Escherichia coli to strong selection by phage U136B to obtain 27 independent mucoid mutants. Mucoidy is a phenotype that results from excess exopolysaccharide and can act as a barrier against viral infection but can also interfere with other cellular functions. We quantified the mutants' phage resistance using efficiency of plaquing assays and swimming motility using swim agar plates, and we sequenced the complete genomes of all mutants to identify mucoid-causing mutations. Increased phage resistance co-occurred with decreased motility. This relationship was mediated by highly parallel (27/27) mutations to the Rcs phosphorelay pathway, which senses membrane stress to regulate exopolysaccharide production. Together, these results provide an empirical example of a pleiotropic relationship between two traits with intermediate genetic complexity.202439194382
8675170.9748Adaptive Strategies in a Poly-Extreme Environment: Differentiation of Vegetative Cells in Serratia ureilytica and Resistance to Extreme Conditions. Poly-extreme terrestrial habitats are often used as analogs to extra-terrestrial environments. Understanding the adaptive strategies allowing bacteria to thrive and survive under these conditions could help in our quest for extra-terrestrial planets suitable for life and understanding how life evolved in the harsh early earth conditions. A prime example of such a survival strategy is the modification of vegetative cells into resistant resting structures. These differentiated cells are often observed in response to harsh environmental conditions. The environmental strain (strain Lr5/4) belonging to Serratia ureilytica was isolated from a geothermal spring in Lirima, Atacama Desert, Chile. The Atacama Desert is the driest habitat on Earth and furthermore, due to its high altitude, it is exposed to an increased amount of UV radiation. The geothermal spring from which the strain was isolated is oligotrophic and the temperature of 54°C exceeds mesophilic conditions (15 to 45°C). Although the vegetative cells were tolerant to various environmental insults (desiccation, extreme pH, glycerol), a modified cell type was formed in response to nutrient deprivation, UV radiation and thermal shock. Scanning (SEM) and Transmission Electron Microscopy (TEM) analyses of vegetative cells and the modified cell structures were performed. In SEM, a change toward a circular shape with reduced size was observed. These circular cells possessed what appears as extra coating layers under TEM. The resistance of the modified cells was also investigated, they were resistant to wet heat, UV radiation and desiccation, while vegetative cells did not withstand any of those conditions. A phylogenomic analysis was undertaken to investigate the presence of known genes involved in dormancy in other bacterial clades. Genes related to spore-formation in Myxococcus and Firmicutes were found in S. ureilytica Lr5/4 genome; however, these genes were not enough for a full sporulation pathway that resembles either group. Although, the molecular pathway of cell differentiation in S. ureilytica Lr5/4 is not fully defined, the identified genes may contribute to the modified phenotype in the Serratia genus. Here, we show that a modified cell structure can occur as a response to extremity in a species that was previously not known to deploy this strategy. This strategy may be widely spread in bacteria, but only expressed under poly-extreme environmental conditions.201930804904
7731180.9748Biochemical Recurrence in Prostate Cancer Is Associated with the Composition of Lactobacillus: Microbiome Analysis of Prostatic Tissue. Many human pathologies, such as malignancy, are linked with specific bacteria and changes in the constituents of the microbiome. In order to examine the association between an imbalance of bacteria and prostate carcinoma, a comparison of the microbiomes present in patients with biochemical recurrence (BCR) or NO BCR (NBCR) was performed. Additionally, 16S rRNA-based next-generation sequencing was applied to identify the bacterial profiles within these tumors in terms of the bacteria and operational genes present. The percentage average taxonomic composition between the taxa indicated no difference between BCR and NBCR. In addition, alpha and beta diversity indices presented no distinction between the cohorts in any statistical method. However, taxonomic biomarker discovery indicated a relatively higher population of Lactobacillus in the NBCR group, and this finding was supported by PCR data. Along with that, differences in the operational activity of the bacterial genes were also determined. It is proposed that the biochemical recurrence was linked to the quantity of Lactobacillus present. The aim of this study was to investigate the microbiome involved in prostate carcinoma and the potential association between them.202337445601
542190.9748Role of Yops and adhesins in resistance of Yersinia enterocolitica to phagocytosis. Yersinia enterocolitica is a pathogen endowed with two adhesins, Inv and YadA, and with the Ysc type III secretion system, which allows extracellular adherent bacteria to inject Yop effectors into the cytosol of animal target cells. We tested the influence of all of these virulence determinants on opsonic and nonopsonic phagocytosis by PU5-1.8 and J774 mouse macrophages, as well as by human polymorphonuclear leukocytes (PMNs). The adhesins contributed to phagocytosis in the absence of opsonins but not in the presence of opsonins. In agreement with previous results, YadA counteracted opsonization. In every instance, the Ysc-Yop system conferred a significant level of resistance to phagocytosis. Nonopsonized single-mutant bacteria lacking either YopE, -H, -T, or -O were phagocytosed significantly more by J774 cells and by PMNs. Opsonized bacteria were phagocytosed more than nonopsonized bacteria, and mutant bacteria lacking either YopH, -T, or -O were phagocytosed significantly more by J774 cells and by PMNs than were wild-type (WT) bacteria. Opsonized mutants lacking only YopE were phagocytosed significantly more than were WT bacteria by PMNs but not by J774 cells. Thus, YopH, -T, and -O were involved in all of the phagocytic processes studied here but YopE did not play a clear role in guarding against opsonic phagocytosis by J774. Mutants lacking YopP and YopM were, in every instance, as resistant as WT bacteria. Overexpression of YopE, -H, -T, or -O alone did not confer resistance to phagocytosis, although it affected the cytoskeleton. These results show that YopH, YopT, YopO, and, in some instances, YopE act synergistically to increase the resistance of Y. enterocolitica to phagocytosis by macrophages and PMNs.200212117925