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The genus Xanthomonas has been primarily studied for pathogenic interactions with plants. However, besides host and tissue-specific pathogenic strains, this genus also comprises nonpathogenic strains isolated from a broad range of hosts, sometimes in association with pathogenic strains, and other environments, including rainwater. Based on their incapacity or limited capacity to cause symptoms on the host of isolation, nonpathogenic xanthomonads can be further characterized as commensal and weakly pathogenic. This study aimed to understand the diversity and evolution of nonpathogenic xanthomonads compared to their pathogenic counterparts based on their cooccurrence and phylogenetic relationship and to identify genomic traits that form the basis of a life history framework that groups xanthomonads by ecological strategies. We sequenced genomes of 83 strains spanning the genus phylogeny and identified eight novel species, indicating unexplored diversity. While some nonpathogenic species have experienced a recent loss of a type III secretion system, specifically the hrp2 cluster, we observed an apparent lack of association of the hrp2 cluster with lifestyles of diverse species. We performed association analysis on a large data set of 337 Xanthomonas strains to explain how xanthomonads may have established association with the plants across the continuum of lifestyles from commensals to weak pathogens to pathogens. Presence of distinct transcriptional regulators, distinct nutrient utilization and assimilation genes, transcriptional regulators, and chemotaxis genes may explain lifestyle-specific adaptations of xanthomonads.

Actinomyces organisms reside on mucosal surfaces of the oropharynx and the genitourinary tract. Polymicrobial infections with Actinomyces organisms are increasingly being reported in the literature. Since these infections differ from classical actinomycosis, lacking of specific clinical and imaging findings, slow-growing Actinomyces organisms can be regarded as contaminants or insignificant findings. In addition, only limited knowledge is available about novel Actinomyces species and their clinical relevance. The recent reclassifications have resulted in the transfer of several Actinomyces species to novel genera Bowdeniella, Gleimia, Pauljensenia, Schaalia, or Winkia. The spectrum of diseases associated with specific members of Actinomyces and these related genera varies. In human infections, the most common species are Actinomyces israelii, Schaalia meyeri, and Schaalia odontolytica, which are typical inhabitants of the mouth, and Gleimia europaea, Schaalia turicensis, and Winkia neuii. In this narrative review, the purpose was to gather information on the emerging role of specific organisms within the Actinomyces and related genera in polymicrobial infections. These include Actinomyces graevenitzii in pulmonary infections, S. meyeri in brain abscesses and infections in the lower respiratory tract, S. turicensis in skin-related infections, G. europaea in necrotizing fasciitis and skin abscesses, and W. neuii in infected tissues around prostheses and devices. Increased understanding of the role of Actinomyces and related species in polymicrobial infections could provide improved outcomes for patient care. Key messages Due to the reclassification of the genus, many former Actinomyces species belong to novel genera Bowdeniella, Gleimia, Pauljensenia, Schaalia, or Winkia. Some of the species play emerging roles in specific infection types in humans. Increasing awareness of their clinical relevance as an established or a putative pathogen in polymicrobial infections brings about improved outcomes for patient care. [ABSTRACT FROM AUTHOR]

Background: Due to rising antibiotic-resistant microorganisms, there is a pressing need to screen approved drugs for repurposing and to develop new antibiotics for controlling infections. Current in vitro and ex vivo models have mostly been unsuccessful in establishing in vivo relevance. In this study, we developed a stringent ex vivo-burned porcine skin model with high in vivo relevance to screen topical antimicrobials. Methods: A 3 cm-diameter thermal injury was created on non-sterilized porcine skin using a pressure-monitored and temperature-controlled burn device. Commensals were determined pre- and post-burn. The burn wound was inoculated with a target pathogen, and efficacies of Silvadene, Flammacerium, Sulfamylon, and Mupirocin were determined. The in vivo relevance of this platform was evaluated by comparing the ex vivo treatment effects to available in vivo treatment outcomes (from our laboratory and published reports) against selective burn pathogens. Results: Approximately 1% of the commensals survived the skin burn, and these commensals in the burn wounds affected the treatment outcomes in the ex vivo screening platform. When tested against six pathogens, both Silvadene and Flammacerium treatment exhibited ~1–3 log reduction in viable counts. Sulfamylon and Mupirocin exhibited higher efficacy than both Silvadene and Flammacerium against Pseudomonas and Staphylococcus, respectively. The ex vivo treatment outcomes of Silvadene and Flammacerium against Pseudomonas were highly comparable to the outcomes of the in vivo (rats). Conclusions: The ex vivo model developed in our lab is a stringent and effective platform for antimicrobial activity screening. The outcome obtained from this ex vivo model is highly relevant to in vivo. [ABSTRACT FROM AUTHOR]

HPV-associated dermatological diseases include benign lesions like cutaneous warts and external genital warts. In addition, HPV infection is associated with the development of epithelial skin cancers, in particular cutaneous squamous cell carcinoma (cSCC). In contrast to anogenital and oropharyngeal cancers caused by mucosal HPV types of genus alpha papillomavirus, cSCC-associated HPV types belong to the genus beta papillomavirus. Currently available HPV vaccines that target mucosal HPV types associated with anogenital cancer and genital warts are type-specific and provide no cross-protection against beta HPV. When implementing vaccination to beta HPV to prevent skin tumors, it must be considered that acquisition of these HPV types occurs early in childhood and that the risk for cSCC increases with growing age and decreasing immune surveillance. Thus, individuals considered for beta HPV vaccination usually have pre-existing infection and are largely immunocompromised. On the other hand, worldwide increasing incidence rates of epithelial skin cancer reflect an urgent need for skin cancer prevention measures. Based on the pathogenic involvement of beta HPV, vaccination may represent a promising prevention strategy. Indeed, various procedures of prophylactic and therapeutic vaccination have been developed, and some of them have shown efficiency in animal models. Thus far, however, none of these vaccine candidates has been approved for application in humans. [ABSTRACT FROM AUTHOR]

Roof rats (Rattus rattus) are a successful invasive species worldwide because of their ability to exploit their commensal relationship with humans. They are opportunistic feeders that use a wide range of natural and anthropogenic food sources. Because some rodent control methods, such as traps and rodenticides, threaten non-target wildlife species, understanding the diets of roof rats can help develop targeted approaches to better control these pests. Our aim is to use stable isotope analysis and stomach contents analysis to determine the diets of roof rats collected in agricultural, urban, and suburban areas in California. We hypothesized that diets of roof rats trapped in agricultural areas would contain crop plants and food resources associated with the agricultural environ­ment (arthropods, mollusks), whereas those from urban and suburban areas, e.g., schools, residential zones, would consume a broader range of food sources, including anthropogenic foods such as pet food, trash, and produce from gardens and fruit trees. To date, we have obtained roof rat carcasses from control efforts across the state, including our own trapping in southern California. Rats were frozen until they could be dissected in the lab. From each rat, we removed the gastrointestinal tract and took a small sample of ear tissue for stable isotope analysis; all tissues were stored in 95% ethanol. Ear tissue samples were dried, cut into small pieces, and weighed before sending them to the UC Davis Stable Isotope Facility for stable carbon (C) and nitrogen (N) isotope analysis. Stomachs were dissected under a dissecting microscope and food items were identified using reference keys. Preliminary analyses of stomach contents revealed significant amounts of what appears to be plant material, seeds, arthropod parts, and rodenticide bait, as well as many roundworms. Isotopic analysis of ear tissue of 64 rats from four Central Valley counties and urban/suburban rats from three southern California counties (n = 65) and Yolo County (n = 14) showed that δ13C values of rats from urban settings were significantly enriched compared to rural rats (Figure 1; F = 4.52, d.f. = 1, 141, P = 0.053), which is consistent with an urban diet containing more anthropogenic foods. δ13C values of urban roof rats were also much more variable (coefficient-of-variation, CV = 8.7%) than that of rats from agricultural areas (CV = 3.6%), which showed remarkably little variation within a site, indicative of feeding on a concentrated, shared resource. δ15N of rats differed significantly between agricultural counties (F = 195.9, d.f. = 3, 60, P

Abstract Commensal Neisseria (Nc) mainly occupy the oropharynx of humans and animals. These organisms do not typically cause disease; however, they can act as a reservoir for antimicrobial resistance genes that can be acquired by pathogenic Neisseria species. This study characterised the carriage and antimicrobial susceptibility profiles of Nc from the oropharynx of 50 participants. Carriage prevalence of Nc species was 86% with 66% of participants colonised with more than one isolate. Isolates were identified by MALDI-ToF and the most common species was N. subflava (61.4%). Minimum inhibitory concentrations (MICs) to penicillin, ceftriaxone, ciprofloxacin, azithromycin, tetracycline, and gentamicin were determined by agar dilution and E-test was used for cefixime. Using Ng CLSI/EUCAST guidelines, Nc resistance rates were above the WHO threshold of 5% resistance in circulating strains for changing the first line treatment empirical antimicrobial: 5% (CLSI) and 13 (EUCAST) for ceftriaxone and 29.3% for azithromycin. Whole genome sequencing of 30 Nc isolates was performed, which identified AMR genes to macrolides and tetracycline. Core gene MLST clustered Nc into three main groups. Gonococcal DNA uptake sequences were identified in two Nc clusters. This suggests that Nc have the potential AMR gene pool and transfer sequences that can result in resistance transfer to pathogenic Neisseria within the nasopharyngeal niche.

Helicobacter pylori infection is usually acquired during childhood and represents one of the most common infections in humans. It is well known that H. pylori has belonged to humankind for hundreds of thousands of years and it accompanied the human migration from Africa. The adult international guidelines recommend treating all infected patients as H. pylori was classified among the first‐class human carcinogens by the WHO in 1994 and it is one of the main factors involved in the development of gastric cancer. Conversely, the pediatric international guidelines are more restrictive in recommending the eradication of the infection in children. Although many studies have shown evidence regarding the pathological role of H. pylori regardless of the age of the infected patients, many others have highlighted its protective/positive role in several extra‐gastric diseases in children. In this review, both points of view regarding the eradication in children are critically analyzed. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent research has helped us understand more about the role of microbes in the health and disease of the lungs. The detection of microbes and microbial products in sputum may improve early lung cancer diagnosis. The monitoring of the microbiome of the lungs over time may help predict the response to and side effects of treatment. However, studies have not yet examined how diet and air pollution affect the lung microbiome and how it might be linked to the development and progression of lung cancer. By examining the lung microbiome, dietary patterns, and air pollutants, we hope to prevent and manage lung cancer in the future. The past several years have provided a more profound understanding of the role of microbial species in the lung. The respiratory tract is a delicate ecosystem of bacteria, fungi, parasites, and viruses. Detecting microbial DNA, pathogen-associated molecular patterns (PAMPs), and metabolites in sputum is poised to revolutionize the early diagnosis of lung cancer. The longitudinal monitoring of the lung microbiome holds the potential to predict treatment response and side effects, enabling more personalized and effective treatment options. However, most studies into the lung microbiota have been observational and have not adequately considered the impact of dietary intake and air pollutants. This gap makes it challenging to establish a direct causal relationship between environmental exposure, changes in the composition of the microbiota, lung carcinogenesis, and tumor progression. A holistic understanding of the lung microbiota that considers both diet and air pollutants may pave the way to improved prevention and management strategies for lung cancer. [ABSTRACT FROM AUTHOR]

Candida species primarily exist as harmless commensals in the gastrointestinal tract of warm-blooded animals. However, they can also cause life-threatening infections, which are often associated with gut microbial dysbiosis. Identifying the microbial actors that restrict Candida to commensalism remains a significant challenge. In vitro models could enable a mechanistic study of the interactions between Candida and simulated colon microbiomes. Therefore, this study aimed to elucidate the spatial and temporal colonization kinetics of specific Candida , including C. albicans, C. tropicalis , and C. parapsilosis , and their relative Nakaseomyces glabratus , by using an adapted SHIME® model, simulating the ileum, and proximal and distal colons. We monitored fungal and bacterial colonization kinetics under conditions of eubiosis (commensal lifestyle) and antibiotic-induced dysbiosis (pathogenic lifestyle). Our findings highlighted the variability in the colonization potential of Candida species across different intestinal regions. The ileum compartment proved to be the most favourable environment for C. albicans and C. parapsilosis under conditions of eubiosis. Antibiotic-induced dysbiosis resulted in resurgence of opportunistic Candida species, especially C. tropicalis and C. albicans. Future research should focus on identifying specific bacterial species influencing Candida colonization resistance and explore the long-term effects of antibiotics on the mycobiome and bacteriome. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus possesses sar family genes, including sarA, S, R, T, U, V, X, Y, Z, and rot, which are transcription factors involved in biofilm formation and quorum sensing. In contrast, Staphylococcus epidermidis has sarA, R, V, X, Y, Z, and rot genes; specifically, SarA, Z, and X are involved in biofilm formation. The expression of the sar family members in S. epidermidis isolated from clinical and non-clinical environments is unknown. This study aimed to establish if clinical and non-clinical isolates of S. epidermidis express the sar family members. We genotyped isolates from clinical ocular infections (n = 52), or non-clinical healthy conjunctiva (n = 40), and healthy skin (n = 50), using multilocus sequence typing (MLST) and the staphylococcal chromosomal cassette mec (SCCmec). We selected strains with different genotypes and representatives of each source of isolation, and the presence of the sar family genes was detected using PCR and RT-qPCR to determine their expression. The sar family genes were present in all selected strains, with no observed differences. The relative expression of the sar family showed that all selected strains expressed each gene weakly, with no significant differences observed between them or between different sources of isolation. In conclusion, the presence and relative expression of the sar family genes are very similar among strains, with no differences based on their origin of isolation and genotype. [ABSTRACT FROM AUTHOR]

ABSTRACTEthanolamine is an abundant compound in the gastrointestinal tract and a valuable source of carbon and nitrogen for pathogenic bacteria harboring ethanolamine utilization (eut) genes. Eut-positive pathogens can consume free ethanolamine to outcompete commensal microbes, which often lack eut genes, and establish infection. Ethanolamine can also act as a host recognition signal for eut-positive pathogens to upregulate virulence genes during colonization. Therefore, reducing free ethanolamine titers may represent a novel approach to preventing infection by eut-positive pathogens. Interestingly, the commensal microorganism Levilactobacillus brevis ATCC 14869 was found to encode over 18 eut genes within its genome. This led us to hypothesize that L. brevis can compete with eut-positive pathogens by clearing free ethanolamine from the environment. Our results demonstrate that despite being unable to metabolize ethanolamine under most conditions, L. brevis ATCC 14869 responds to the compound by increasing the expression of genes encoding proteins involved in microcompartment formation and adhesion to the intestinal epithelial barrier. The improved intestinal adhesion of L. brevis in the presence of ethanolamine also enhanced the exclusion of eut-positive pathogens from adhering to intestinal epithelial cells. These findings support further studies to test whether L. brevis ATCC 14869 can counter enteric pathogens and prevent or reduce the severity of infections. Overall, the metabolic capabilities of L. brevis ATCC 14869 offer a unique opportunity to add to the armamentarium of antimicrobial therapies as well as our understanding of the mechanisms used by beneficial microbes to sense and adapt to host microenvironments.

Background: Surgical site infections (SSIs) can be caused by various factors, including contamination of the surgical field. Perioperative cultures can be employed in clean orthopedic procedures to detect bacterial contamination that may occur during surgery. Aims and Objectives: The study aimed to evaluate the correlation between suction tip cultures and surgical wounds in clean orthopedic surgeries. Materials and Methods: A cross-sectional study was conducted at Yenepoya Medical College Hospital, Mangalore, Karnataka, with 250 patients in whom drain tips were sent for culture and followed up for 3 months to assess for SSI. Skin commensals from the nasal and groin samples were analyzed for the presence of bacteria. Results: A total of 250 patients meeting the inclusion and exclusion criteria were included. Thirty patients were positive for drain tip culture, and 12 (4.8%) patients had SSI during the 3rd month follow-up period, showing a statistically significant relationship between drain tip culture and SSIs (P=0.001). Skin commensals constituted 67% (nasal) and 100% in the groin of perioperative contaminants, accounting for 4.8% of SSIs. Conclusion: Suction drain tip culture and skin commensal analysis may be good predictors of SSIs. Intraoperative surgical site contaminants can be identified using perioperative cultures. Timely administration of suitable antibiotics and local wound care for perioperative contamination can help minimize the incidence of SSI.

Background: Surgical site infections (SSIs) can be caused by various factors, including contamination of the surgical field. Perioperative cultures can be employed in clean orthopedic procedures to detect bacterial contamination that may occur during surgery. Aims and Objectives: The study aimed to evaluate the correlation between suction tip cultures and surgical wounds in clean orthopedic surgeries. Materials and Methods: A cross-sectional study was conducted at Yenepoya Medical College Hospital, Mangalore, Karnataka, with 250 patients in whom drain tips were sent for culture and followed up for 3 months to assess for SSI. Skin commensals from the nasal and groin samples were analyzed for the presence of bacteria. Results: A total of 250 patients meeting the inclusion and exclusion criteria were included. Thirty patients were positive for drain tip culture, and 12 (4.8%) patients had SSI during the 3rd month follow-up period, showing a statistically significant relationship between drain tip culture and SSIs (P=0.001). Skin commensals constituted 67% (nasal) and 100% in the groin of perioperative contaminants, accounting for 4.8% of SSIs. Conclusion: Suction drain tip culture and skin commensal analysis may be good predictors of SSIs. Intraoperative surgical site contaminants can be identified using perioperative cultures. Timely administration of suitable antibiotics and local wound care for perioperative contamination can help minimize the incidence of SSI. [ABSTRACT FROM AUTHOR]

The study was conducted to identify cluster patterns of enteric microorganisms with potential etiological relevance for infectious gastroenteritis in stool samples of individuals from Ghana, which is a known high-endemicity setting for infectious gastroenteritis. These patterns were compared to previous observations with specimens from Colombian indigenous people in order to assess potentially stable clustering for temporally and spatially distinct populations from high-endemicity regions. By doing so, the study aimed to identify stable clusters as markers of microbial interaction with potential importance for etiological relevance assignment in cases of multiple enteric pathogen detections. Stool samples from 1569 Ghanaian individuals (875 from HIV patients, 30 from HIV-negative control adult patients, and 644 from children < 2 years of age) were assessed for enteric microorganisms by applying real-time PCR. As a result, nucleic acids of bacterial microorganisms were most frequently detected, followed by protozoa, microsporidia, and helminths. Interestingly, the cluster assessment confirmed interaction patterns known from the previous analysis with Colombian indigenous people, demonstrating a high likelihood of Blastocystis hominis for clustering with other microorganisms and a prominent, potentially mediating role of Dientamoeba fragilis for microbial interactions within the clusters. In conclusion, the assessment confirmed conserved clustering of enteric microorganisms with potential etiological relevance for human infectious gastroenteritis over geographically distinct high-endemicity settings. Furthermore, the composition of abundant microorganisms is more important than regional factors for the determination of the interplay of enteric microorganisms in the human gut. Thereby, some microbial pathogens and commensals seem more susceptible to a changing microbial composition in the human gut than others. [ABSTRACT FROM AUTHOR]

Gopher tortoises (Gopherus polyphemus), the only land tortoises native to the southeastern United States, are found throughout their range in a variety of upland habitat types, with their use of upland pine-dominated habitats receiving most attention. Fewer studies have examined their use of coastal beach dune habitats, but some of the highest gopher tortoise burrow densities have been observed in this vulnerable, yet critical, habitat. Gopher tortoises construct extensive burrows for their own use, and these burrows have also been shown to support numerous other animals (i.e., commensal species) that may depend on them for critical needs (e.g., shelter, food). Motion-activated wildlife cameras allow for nonintrusive and continuous observation of burrow activity with minimal disturbance to the animals and habitat. Here we examined 10 gopher tortoise burrows over a 12-mo period using motion-activated wildlife cameras in beach dune habitat in an undeveloped section of coastline in northeast Florida. Gopher tortoises were most frequently observed during the spring and summer months (April–August), and most often during daylight hours. Gopher tortoise behaviors such as burrow maintenance, mating, foraging, and resting were all observed more during April through August, which is a slightly earlier start than these activities have been observed in inland populations. We observed a commensal community of 51 animal taxa using tortoise burrows and their aprons, 29 of which we were able to identify to species. The commensal community was generally similar to those in inland habitats, but we did observe some taxa that were previously undocumented at gopher tortoise burrows including 2 bird species and 8 insect taxa. These commensals displayed varied diel and seasonal activity patterns, with many taxa observed at burrows concurrently occupied by gopher tortoises. Considered together, our observations of gopher tortoise behavior and their commensal community in coastal beach dunes provide valuable insights into the importance of this understudied habitat and highlight distinct differences from inland ecosystems. [ABSTRACT FROM AUTHOR]

The skin is the outermost organ of the human body and serves as a protective barrier against external pathogens and environmental factors. It is colonised by a diverse community of microorganisms, collectively known as the skin microbiome. From birth to death, the skin undergoes dynamic changes in microbial composition influenced by endogenous physiological host factors, environmental exposure and various diseases. These microorganisms play a crucial role in maintaining the health and functionality of the skin. They contribute to the education and moderation of the immune system, protect against pathogenic invaders and regulate various physiological processes, such as maintaining a healthy barrier. Dysbiosis, characterised by microbial imbalance, is associated with various skin disorders, among others atopic dermatitis and acne vulgaris. In recent years, interest has been growing in understanding the role of the skin microbiome in health and disease. Understanding these complex interactions has led to the development of novel therapeutic approaches that target the skin microbiome, including prebiotic and probiotic therapy. This article provides an overview of the current knowledge of the skin microbiome and its impact on human health and disease. [ABSTRACT FROM AUTHOR]

ABSTRACT Haemophilus parainfluenzae (Hp) is a Gram-negative, highly prevalent, and abundant commensal in the human oral cavity, and an infrequent extraoral opportunistic pathogen. Hp occupies multiple niches in the oral cavity, including the supragingival plaque biofilm. Little is known about how Hp interacts with its neighbors in healthy biofilms nor its mechanisms of pathogenesis as an opportunistic pathogen. To address this, we identified the essential genome and conditionally essential genes in in vitro biofilms aerobically and anaerobically. Using transposon insertion sequencing (TnSeq) with a highly saturated mariner transposon library in two strains, the ATCC33392 type-strain (Hp 392) and oral isolate EL1 (Hp EL1), we show that the essential genomes of Hp 392 and Hp EL1 are composed of 395 (20%) and 384 (19%) genes, respectively. The core essential genome, consisting of 341 (17%) essential genes conserved between both strains, was composed of genes associated with genetic information processing, carbohydrate, protein, and energy metabolism. We also identified conditionally essential genes for aerobic and anaerobic biofilm growth, which were associated with carbohydrate and energy metabolism in both strains. RNAseq analysis determined that most genes upregulated during anaerobic growth are not essential for Hp 392 anaerobic survival. The completion of this library and analysis under these conditions gives us a foundational insight into the basic biology of H. parainfluenzae in differing oxygen conditions, similar to its in vivo habitat. This library presents a valuable tool for investigation into conditionally essential genes for an organism that lives in close contact with many microbial species in the human oral habitat.IMPORTANCEHaemophilus parainfluenzae is a highly abundant human commensal microbe, present in most healthy individuals where it colonizes the mouth. H. parainfluenzae correlates with good oral health and may play a role in preservation of healthy host status. Also, H. parainfluenzae can cause opportunistic infections outside of the oral cavity. To date, little is known about how H. parainfluenzae colonizes the human host, despite being such a frequent and abundant part of our human microbiome. Here, we demonstrate the creation and use of a powerful tool, a TnSeq library, used to identify genes necessary for both the outright growth of this organism and also genes conditionally essential for growth in varying oxygen status which it can encounter in the human host. This tool and these data serve as a foundation for further study of this relatively unknown organism that may play a role in preserving human health.

Background: Due to rising antibiotic-resistant microorganisms, there is a pressing need to screen approved drugs for repurposing and to develop new antibiotics for controlling infections. Current in vitro and ex vivo models have mostly been unsuccessful in establishing in vivo relevance. In this study, we developed a stringent ex vivo-burned porcine skin model with high in vivo relevance to screen topical antimicrobials. Methods: A 3 cm-diameter thermal injury was created on non-sterilized porcine skin using a pressure-monitored and temperature-controlled burn device. Commensals were determined pre- and post-burn. The burn wound was inoculated with a target pathogen, and efficacies of Silvadene, Flammacerium, Sulfamylon, and Mupirocin were determined. The in vivo relevance of this platform was evaluated by comparing the ex vivo treatment effects to available in vivo treatment outcomes (from our laboratory and published reports) against selective burn pathogens. Results: Approximately 1% of the commensals survived the skin burn, and these commensals in the burn wounds affected the treatment outcomes in the ex vivo screening platform. When tested against six pathogens, both Silvadene and Flammacerium treatment exhibited ~1–3 log reduction in viable counts. Sulfamylon and Mupirocin exhibited higher efficacy than both Silvadene and Flammacerium against Pseudomonas and Staphylococcus, respectively. The ex vivo treatment outcomes of Silvadene and Flammacerium against Pseudomonas were highly comparable to the outcomes of the in vivo (rats). Conclusions: The ex vivo model developed in our lab is a stringent and effective platform for antimicrobial activity screening. The outcome obtained from this ex vivo model is highly relevant to in vivo.

At a rapid pace, biologists are learning the many ways in which resident microbes influence, and sometimes even control, their hosts to shape both health and disease. Understanding the biochemistry behind these interactions promises to reveal completely novel and targeted ways of counteracting disease processes. However, in our protocols and publications, we continue to describe these new results using a language that originated in a completely different context. This language developed when microbial interactions with hosts were perceived to be primarily pathogenic, as threats that had to be vanquished. Biomedicine had one dominating thought: winning this war against microorganisms. Today, we know that beyond their defensive roles, host tissues, especially epithelia, are vital to ensuring association with the normal microbiota, the communities of microbes that persistently live with the host. Thus, we need to adopt a language that better encompasses the newly appreciated importance of host-microbiota associations. We also need a language that frames the onset and progression of pathogenic conditions within the context of the normal microbiota. Such a reimagined lexicon should make it clear, from the very nature of its words, that microorganisms are primarily vital to our health, and only more rarely the cause of disease. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'. [ABSTRACT FROM AUTHOR]

Prior to the present study, 11 genera and 16 species of pinnotherid crabs were known from Australia, of which two species of the genus Arcotheres were recorded: Arcotheres boninensis and A. similis. The current study extends our knowledge of Australian Arcotheres in a species new to science, significant range extensions for A. boninensis in Australia, and the first national record of A. exiguus. The new species (A. eclecticus) is closest to Arcotheres palaensis , but differs chiefly in features of the carapace. Arcotheres boninensis was formerly known from Western Australia and is now known to span all of northern Australia. To date, A. exiguus has been recorded from the Philippines westwards to Singapore, Malaysia and India; first records from Australia and Hong Kong represent the southern- and northernmost records of the species, respectively. The Australian pinnotherid fauna now stands at 11 genera and 18 species, of which four species belong to Arcotheres. A key to the Australian species of Arcotheres is provided. [ABSTRACT FROM AUTHOR]

Presented here are the results of archaeoparasitological analysis of habitation layers at Shag River Mouth, Otago coast. Two types of helminth eggs were identified: The first type is Toxocara canis, associated with the introduced kurī dog (Canis familiaris), which could have adversely affected local people and their dogs. The other type very closely resembles that of Stringopotaenia psittacea, associated with the critically endangered endemic kākāpō (Strigops habroptilus) parrot. The results represent the first South Island archaeo parasitological identifications. There was no starch or associated material in the samples, such as introduced Polynesian crops and indigenous starchy Māori food plants. This lack is consistent with the interpretation of the site as that of a transient village focused on big game hunting. [ABSTRACT FROM AUTHOR]

Actinomycosis, an oral cavity commensal, causes cervicofacial infection in patients associated with an immunosuppression state and local mucosal injuries. Bone involvement by this commensal is rare. In the present case, we report a case of left peri mandibular soft tissue, soft to firm, tender swelling in a 39‐year‐old immunocompetent male diagnosed as Actinomycosis infection on fine needle aspiration cytology (FNAC) and cell block preparation. [ABSTRACT FROM AUTHOR]

Resident microbes in skin and gut predominantly impact local immune cell function during homeostasis. However, colitis-associated neutrophilic skin disorders suggest possible breakdown of this compartmentalization with disease. Using a model wherein neonatal skin colonization by Staphylococcus epidermidis facilitates generation of commensal-specific tolerance and CD4+ regulatory T cells (Tregs), we ask whether this response is perturbed by gut inflammation. Chemically induced colitis is accompanied by intestinal expansion of S. epidermidis and reduces gut-draining lymph node (dLN) commensal-specific Tregs. It also results in reduced commensal-specific Tregs in skin and skin-dLNs and increased skin neutrophils. Increased CD4+ circulation between gut and skin dLN suggests that the altered cutaneous response is initiated in the colon, and resistance to colitis-induced effects in Cd4creIl1r1fl/fl mice implicate interleukin (IL)-1 in mediating the altered commensal-specific response. These findings provide mechanistic insight into observed connections between inflammatory skin and intestinal diseases.

We report the second world observation of the bizarre nematode-parasitic fungus-like organism, Spirogyromyces vermicola, from forest soil at Saltillo, Mexico. It is a benign parasite of nematodes that fills their intestine. Its phylogenetic position remains a mystery, but its morphology and development are reminiscent of Harpellales and Orphellales in the Kickxellomycotina. Spirogyromyces was cultivated in vivo in the original host (Rhabditis) and in Caenorhabditis elegans. Spirogyromyces proliferated in both hosts, and it did not appear to affect significantly health, reproduction, or numbers of hosts. The rediscovery of Spirogyromyces will highlight its potential in the study of parasitic systems in nematodes, including Caenorhabditis research.

Enterococcus faecalis is a bacterium which accompanies us from the first days of our life. As a commensal it produces vitamins, metabolizes nutrients, and maintains intestinal pH. All of that happens in exchange for a niche to inhabit. It is not surprising then, that the bacterium was and is used as an element of many probiotics and its positive impact on the human immune system and the body in general is hard to ignore. This bacterium has also a dark side though. The plasticity and relative ease with which one acquires virulence traits, and the ability to hide from or even deceive and use the immune system to spread throughout the body make E. faecalis a more and more dangerous opponent. The statistics clearly show its increasing role, especially in the case of nosocomial infections. Here we present the summarization of current knowledge about E. faecalis, especially in the context of its relations with the human immune system. [ABSTRACT FROM AUTHOR]

Mucochytrium quahogii, also known as QPX or Quahog Parasite Unknown, is the causative agent of QPX disease in the hard clam (Mercenaria mercenaria). Host–pathogen–environment interactions between M. quahogii, the hard clam, and temperature were explored in a microcosm experiment. Hard clams were housed in individual tanks with sterile seawater under two temperature regimes: low (13 °C) temperature, which is thought to be optimal for QPX disease development, and high (20 °C) temperature, which has been shown to promote "healing" of QPX-infected clams. Hard clam tissue, pallial fluid, seawater, and shell biofilms were collected and assayed for M. quahogii. The release of M. quahogii from naturally infected live hard clams into seawater was detected only in the low temperature treatment, suggesting that temperature influences the release of potentially infectious cells. M. quahogii was commonly found in hard clam pallial fluid, even after 9 weeks in the lab, suggesting pallial fluid is a stable reservoir of M. quahogii within its primary host and that M. quahogii is not a transient component of the hard clam microbiota. Overall, results support a host-specific relationship and that M. quahogii is a commensal member of the hard clam microbiota, supporting its classification as an opportunistic pathogen. [ABSTRACT FROM AUTHOR]

Enterococcus faecium (Efm) is a versatile pathogen, responsible for multidrug-resistant infections, especially in hospitalized immunocompromised patients. Its population structure has been characterized by diverse clades (A1, A2, and B (reclassified as E. lactis (Ela)), adapted to different environments, and distinguished by their resistomes and virulomes. These features only partially explain the predominance of clade A1 strains in nosocomial infections. We investigated in vitro interaction of 50 clinical isolates (clade A1 Efm) against 75 commensal faecal isolates from healthy humans (25 clade A2 Efm and 50 Ela). Only 36% of the commensal isolates inhibited clinical isolates, while 76% of the clinical isolates inhibited commensal isolates. The most apparent overall differences in inhibition patterns were presented between clades. The inhibitory activity was mainly mediated by secreted, proteinaceous, heat-stable compounds, likely indicating an involvement of bacteriocins. A custom-made database targeting 76 Bacillota bacteriocins was used to reveal bacteriocins in the genomes. Our systematic screening of the interactions between nosocomial and commensal Efm and Ela on a large scale suggests that, in a clinical setting, nosocomial strains not only have an advantage over commensal strains due to their possession of AMR genes, virulence factors, and resilience but also inhibit the growth of commensal strains. [ABSTRACT FROM AUTHOR]

Few data outside of individual case reports are available on non-meningococcal, non-gonococcal species of Neisseria as causative agents of invasive disease. This review collates disease, organism and patient information from case reports on the topic. A literature search was performed examining articles describing diseases caused by non-meningococcal and non-gonococcal Neisseria. Neisseria present as opportunistic pathogens causing a wide variety of diseases including serious presentations, endocarditis being the most common condition described and N. mucosa the most commonly presenting pathogen overall. Disease may occur in otherwise healthy patients, although risk factors for infection include recent surgery, an immunocompromised state, poor oral health, and intravenous drug use. Commensal Neisseria infections are rare but can present serious invasive diseases. Further research is required to determine why some species cause disease more than others or why some are inclined towards particular manifestations. [ABSTRACT FROM AUTHOR]

The study was conducted to identify cluster patterns of enteric microorganisms with potential etiological relevance for infectious gastroenteritis in stool samples of individuals from Ghana, which is a known high-endemicity setting for infectious gastroenteritis. These patterns were compared to previous observations with specimens from Colombian indigenous people in order to assess potentially stable clustering for temporally and spatially distinct populations from high-endemicity regions. By doing so, the study aimed to identify stable clusters as markers of microbial interaction with potential importance for etiological relevance assignment in cases of multiple enteric pathogen detections. Stool samples from 1569 Ghanaian individuals (875 from HIV patients, 30 from HIV-negative control adult patients, and 644 from children < 2 years of age) were assessed for enteric microorganisms by applying real-time PCR. As a result, nucleic acids of bacterial microorganisms were most frequently detected, followed by protozoa, microsporidia, and helminths. Interestingly, the cluster assessment confirmed interaction patterns known from the previous analysis with Colombian indigenous people, demonstrating a high likelihood of Blastocystis hominis for clustering with other microorganisms and a prominent, potentially mediating role of Dientamoeba fragilis for microbial interactions within the clusters. In conclusion, the assessment confirmed conserved clustering of enteric microorganisms with potential etiological relevance for human infectious gastroenteritis over geographically distinct high-endemicity settings. Furthermore, the composition of abundant microorganisms is more important than regional factors for the determination of the interplay of enteric microorganisms in the human gut. Thereby, some microbial pathogens and commensals seem more susceptible to a changing microbial composition in the human gut than others.

ABSTRACT Polymicrobial airway infections in persons with cystic fibrosis (pwCF) can positively or negatively impact the course of disease. A major CF pathogen, Pseudomonas aeruginosa, often establishes a chronic infection leading to lung deterioration. Interestingly, the presence of certain oral commensal streptococci is correlated with improved outcomes for pwCF. We previously reported that hydrogen peroxide production by these commensals combined with nitrite generates reactive nitrogen intermediates (RNI), which inhibit P. aeruginosa in vitro. In this study, we utilized a rat co-infection lung model to assess whether oral commensal-generated RNI can restrict the pathogenesis of a CF isolate of P. aeruginosa. We report that the oral commensal Streptococcus parasanguinis and nitrite reduce P. aeruginosa-induced host inflammation in wild-type rats. To better recapitulate CF-specific airway conditions, we used a bronchial epithelial cell culture model to gain a better understanding of how S. parasanguinis and nitrite may influence P. aeruginosa burden during a CF infection. Hence, we co-infected wild-type and cystic fibrosis transconductance regulator (CFTR) channel-deficient bronchial epithelial cells with P. aeruginosa and S. parasanguinis with or without nitrite. Strikingly, S. parasanguinis reduced the bacterial burden of P. aeruginosa without nitrite, promoted epithelial cell viability, and stimulated nitrite production in the wild-type and CFTR-deficient epithelial cells, where nitrite induction was more apparent in the CFTR mutant cells. Taken together, our study demonstrates that the commensal S. parasanguinis may provide protection against P. aeruginosa-induced inflammation and cell death, as well as modulate nitrite flux in airway epithelial cells. IMPORTANCE Respiratory infections are a leading cause of morbidity and mortality in people with cystic fibrosis (CF). These infections are polymicrobial in nature with overt pathogens and other colonizing microbes present. Microbiome data have indicated that the presence of oral commensal bacteria in the lungs is correlated with improved outcomes. We hypothesize that one oral commensal, Streptococcus parasanguinis, inhibits CF pathogens and modulates the host immune response. One major CF pathogen is Pseudomonas aeruginosa, a Gram-negative, opportunistic bacterium with intrinsic drug resistance and an arsenal of virulence factors. We have previously shown that S. parasanguinis inhibits P. aeruginosa in vitro in a nitrite-dependent manner through the production of reactive nitrogen intermediates. In this study, we demonstrate that while this mechanism is evident in a cell culture model of the CF airway, an alternative mechanism by which S. parasanguinis may improve outcomes for people with CF is through immunomodulation.

The abundance of gut commensals has historically been associated with health-promoting effects despite the fact that the definition of good or bad microbiota remains condition-specific. The beneficial or pathogenic nature of microbiota is generally dictated by the dimensions of host-microbiota and microbe-microbe interactions. With the increasing popularity of gut microbiota in human health and disease, emerging evidence suggests opportunistic infections promoted by those gut bacteria that are generally considered beneficial. Therefore, the current review deals with the opportunistic nature of the gut commensals and aims to summarise the concepts behind the occasional commensal-to-pathogenic transformation of the gut microbes. Specifically, relevant clinical and experimental studies have been discussed on the overgrowth and bacteraemia caused by commensals. Three key processes and their underlying mechanisms have been summarised to be responsible for the opportunistic nature of commensals, viz. improved colonisation fitness that is dictated by commensal-pathogen interactions and availability of preferred nutrients; pathoadaptive mutations that can trigger the commensal-to-pathogen transformation; and evasion of host immune response as a survival and proliferation strategy of the microbes. Collectively, this review provides an updated concept summary on the underlying mechanisms of disease causative events driven by gut commensal bacteria. [ABSTRACT FROM AUTHOR]

Tritrichomonas muris is a common flagellated protist isolated from the cecum of wild rodents. This commensal protist has been shown previously to alter immune phenotypes in laboratory mice. Other trichomonads, referred to as Tritrichomonas musculis and Tritrichomonas rainier, also naturally colonize laboratory mice and cause immune alterations. This report formally describes two new trichomonads, Tritrichomonas musculus n. sp., and Tritrichomonas casperi n. sp., at the ultrastructural and molecular level. These two protists were isolated from laboratory mice and were differentiated by their size and the structure of their undulating membrane and posterior flagellum. Analysis at the 18S rRNA and trans‐ITS genetic loci supported their designation as distinct species, related to T. muris. To assess the true extent of parabasalid diversity infecting laboratory mice, 135 mice bred at the National Institutes of Health (NIH) were screened using pan‐parabasalid primers that amplify the trans‐ITS region. Forty‐four percent of mice were positive for parabasalids, encompassing a total of eight distinct sequence types. Tritrichomonas casperi and Trichomitus‐like protists were dominant. T. musculus and T. rainier were also detected, but T. muris was not. Our work establishes a previously underappreciated diversity of commensal trichomonad flagellates that naturally colonize the enteric cavity of laboratory mice. [ABSTRACT FROM AUTHOR]

The response of patients to immunotherapy can vary significantly due to differences in their gut and tumor microbiomes. Gut bacteria play a crucial role in shaping the host immune system, tumor immunity, and response to immunotherapy, which makes them key predictors and targets for immunotherapy. Bacteria can also colonize and persist within tumor cells, affecting cancer initiation, progression, metastasis, and treatment response. The specific gut and tumor composition of bacteria can robustly predict the clinical outcomes and adverse effects. Diet, prebiotics, probiotics, metabolites, and antibiotics that have an impact on the microbiome influence the response to immunotherapy. Manipulating the microbiome remains challenging as we lack a complete understanding of the modes of action of the tumor and gut microbiomes. The past decade has witnessed a revolution in cancer treatment by shifting from conventional therapies to immune checkpoint inhibitors (ICIs). These immunotherapies unleash the host immune system against the tumor and have achieved unprecedented durable remission. However, 80% of patients do not respond. This review discusses how bacteria are unexpected drivers that reprogram tumor immunity. Manipulating the microbiota impacts on tumor development and reprograms the tumor microenvironment (TME) of mice on immunotherapy. We anticipate that harnessing commensals and the tumor microbiome holds promise to identify patients who will benefit from immunotherapy and guide the choice of new ICI combinations to advance treatment efficacy. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) in Escherichia coli of animal origin presents a threat to human health. Although animals are not the primary source of human infections, humans may be exposed to AMR E. coli of animal origin and their AMR genes through the food chain, direct contact with animals, and via the environment. For this reason, AMR in E. coli from food producing animals is included in most national and international AMR monitoring programmes and is the subject of a large body of research. As pig farming is one of the largest livestock sectors and the one with the highest antimicrobial use, there is considerable interest in the epidemiology of AMR in E. coli of porcine origin. This literature review presents an overview and appraisal of current knowledge of AMR in commensal E. coli of the porcine gastrointestinal tract with a focus on its evolution during the pig lifecycle and the relationship with antimicrobial use. It also presents an overview of the epidemiology of resistance to extended spectrum cephalosporins, fluoroquinolones, and colistin in pig production. The review highlights the widespread nature of AMR in the porcine commensal E. coli population, especially to the most-used classes in pig farming and discusses the complex interplay between age and antimicrobial use during the pig lifecycle. [ABSTRACT FROM AUTHOR]

Chronic inflammatory periodontal disease develops in part from the infiltration of a large number of classically activated inflammatory macrophages that release inflammatory cytokines important for disease progression, including inflammasome-dependent interleukin (IL)-1β. Streptococcus gordonii is a normally commensal oral microorganism; while not causative, recent evidence indicates that commensal oral microbes are required for the full development of periodontal disease. We have recently reported that inflammatory macrophages counterintuitively allow for the increased survival of phagocytosed S. gordonii over nonactivated or alternatively activated macrophages. This survival is dependent on increased reactive oxygen species production within the phagosome of the inflammatory macrophages, and resistance by the bacterium and can result in S. gordonii damaging the phagolysosomes. Here, we show that activated macrophages infected with live S. gordonii release more IL-1β than non-activated macrophages infected with either live or dead S. gordonii , and that the survival of oral Streptococci are more dependent on macrophage activation than other Gram positive microbes, both classical pathogens and commensals. We also find that S. gordonii –dependent inflammatory macrophage inflammasome activation requires the cytoplasmic NLRP6. Overall, our results suggest S. gordonii is capable of evading immune destruction, increasing inflammatory mediators, and increasing inflammatory macrophage response, and that this ability is increased under conditions of inflammation. This work reveals additional mechanisms by which normally commensal oral streptococci-macrophage interactions can change, resulting in increased release of mature IL-1β, potentially contributing to an environment that perpetuates inflammation. [ABSTRACT FROM AUTHOR]

It is widely accepted that favorable fitness in commensal colonization is one of the prime facilitators of clonal dissemination in bacteria. The question arises as to what kind of fitness advantage may be wielded by uropathogenic strains of the two predominant fluoroquinolone- and multidrug-resistant clonal groups of E. coli—ST131-H30 and ST1193, which has permitted their unprecedented pandemic-like global expansion in the last few decades. The colonization-associated genes' content, carriage of low-cost plasmids, and integrons with weak promoters could certainly contribute to the fitness of the pandemic groups, although those genetic factors are common among other clonal groups as well. Also, ST131-H30 and ST1193 strains harbor fluoroquinolone-resistance conferring mutations targeting serine residues in DNA gyrase (GyrA-S83) and topoisomerase IV (ParC-S80) that, in those clonal backgrounds, might result in a commensal fitness benefit, i.e., beyond the antibiotic resistance per se. This fitness gain might have contributed not only to the widespread dissemination of these major clones in the healthcare setting but also to their long-term colonization of healthy individuals and, thus, circulation in the community, even in a low or no fluoroquinolone use environment. This evolutionary shift affecting commensal E. coli, initiated by mutations co-favorable in both antibiotics-treated patients and healthy individuals warrants more in-depth studies to monitor further changes in the epidemiological situation and develop effective measures to reduce the antibiotic resistance spread. [ABSTRACT FROM AUTHOR]

ABSTRACT Polymicrobial biofilms are present in many environments particularly in the human oral cavity where they can prevent or facilitate the onset of disease. While recent advances have provided a clear picture of both the constituents and their biogeographic arrangement, it is still unclear what mechanisms of interaction occur between individual species in close proximity within these communities. In this study, we investigated two mechanisms of interaction between the highly abundant supragingival plaque (SUPP) commensal Corynebacterium matruchotii and Streptococcus mitis which are directly adjacent/attached in vivo. We discovered that C. matruchotii enhanced the fitness of streptococci dependent on its ability to detoxify streptococcal-produced hydrogen peroxide and its ability to oxidize lactate also produced by streptococci. We demonstrate that the fitness of adjacent streptococci was linked to that of C. matruchotii and that these mechanisms support the previously described “corncob” arrangement between these species but that this is favorable only in aerobic conditions. Furthermore, we utilized scanning electrochemical microscopy to quantify lactate production and consumption between individual bacterial cells for the first time, revealing that lactate oxidation provides a fitness benefit to S. mitis not due to pH mitigation. This study describes mechanistic interactions between two highly abundant human commensals that can explain their observed in vivo spatial arrangements and suggest a way by which they may help preserve a healthy oral bacterial community. IMPORTANCE As the microbiome era matures, the need for mechanistic interaction data between species is crucial to understand how stable microbiomes are preserved, especially in healthy conditions where the microbiota could help resist opportunistic or exogenous pathogens. Here we reveal multiple mechanisms of interaction between two commensals that dictate their biogeographic relationship to each other in previously described structures in human supragingival plaque. Using a novel variation for chemical detection, we observed metabolite exchange between individual bacterial cells in real time validating the ability of these organisms to carry out metabolic crossfeeding at distal and temporal scales observed in vivo. These findings reveal one way by which these interactions are both favorable to the interacting commensals and potentially the host.

In humans, many diseases are associated with alterations in gut microbiota, namely increases or decreases in the abundance of specific bacterial groups. One example is the genus Faecalibacterium. Numerous studies have underscored that low levels of Faecalibacterium are correlated with inflammatory conditions, with inflammatory bowel disease (IBD) in the forefront. Its representation is also diminished in the case of several diseases, including colorectal cancer (CRC), dermatitis, and depression. Additionally, the relative presence of this genus is considered to reflect, at least in part, intestinal health status because Faecalibacterium is frequently present at reduced levels in individuals with gastrointestinal diseases or disorders. In this review, we first thoroughly describe updates to the taxonomy of Faecalibacterium , which has transformed a single-species taxon to a multispecies taxon over the last decade. We then explore the links discovered between Faecalibacterium abundance and various diseases since the first IBD-focused studies were published. Next, we examine current available strategies for modulating Faecalibacterium levels in the gut. Finally, we summarize the mechanisms underlying the beneficial effects that have been attributed to this genus. Together, epidemiological and experimental data strongly support the use of Faecalibacterium as a next-generation probiotic (NGP) or live biotherapeutic product (LBP). [ABSTRACT FROM AUTHOR]

Concept of microorganisms has largely been perceived from their pathogenic view point. Nevertheless, it is being gradually revisited in terms of its significance to human health and now appears to be the most dominant force that shapes the immune system of the human body and also determines an individual’s predisposition to diseases. Human inhabits bacterial diversity (which is predominant among all microbial communities in human body) occupying 0.3% of body mass, known as microbiota. On birth, a part of microbiota that child obtains is essentially a mother’s legacy. So, the review was initiated with this critical topic of microbiotal inheritance. Since, each body site has distinct physiological specifications; therefore, they contain discrete microbiome composition that has been separately discussed along with dysbiosis-induced pathologies originating in different body organs. Factors affecting microbiome composition and may cause dysbiosis like antibiotics, delivery, feeding method etc. as well as the strategies that immune system adopts to prevent dysbiosis have been highlighted. We also tried to bring into attention the topic of dysbiosis induced biofilms, that enables cohort to survive stresses, evolve, disseminate and infection resurgence that is still in dormancy. Eventually, we put spotlight on microbiome significance in medical therapeutics. We didn’t merely confine article to gut microbiota, that is being studied more extensively. Numerous community forms at diverse body sites are inter-related, and being exposed to awfully variable perturbations appear to be challenging to evaluate perturbation risks holistically. All aspects have been elaborately discussed to achieve a global depiction of human microbiota in order to meet urgent necessity for protocol standardisation. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa dominates the complex polymicrobial cystic fibrosis (CF) airway and is a leading cause of death in persons with CF. Interestingly, oral streptococcal colonization has been associated with stable CF lung function. The most abundant streptococcal species found in stable patients, Streptococcus salivarius, has been shown to downregulate pro-inflammatory cytokines in multiple colonization models. However, no studies have demonstrated how S. salivarius potentially improves lung function. Our lab previously demonstrated that the P. aeruginosa exopolysaccharide Psl promotes S. salivarius biofilm formation in vitro, suggesting a possible mechanism by which S. salivarius is incorporated into the CF airway microbial community. In this study, we demonstrate that co-infection of rats leads to enhanced S. salivarius colonization and reduced P. aeruginosa colonization. Histological scores for tissue inflammation and damage are lower in dual-infected rats compared to P. aeruginosa infected rats. Additionally, pro-inflammatory cytokines IL-1β, IL-6, CXCL2, and TNF-α are downregulated during co-infection compared to P. aeruginosa single-infection. Lastly, RNA sequencing of cultures grown in synthetic CF sputum revealed that P. aeruginosa glucose metabolism genes are downregulated in the presence of S. salivarius, suggesting a potential alteration in P. aeruginosa fitness during co-culture. Overall, our data support a model in which S. salivarius colonization is promoted during co-infection with P. aeruginosa, whereas P. aeruginosa airway bacterial burden is reduced, leading to an attenuated host inflammatory response. [ABSTRACT FROM AUTHOR]

The host must develop tolerance to commensal microbes and protective responses to infectious pathogens, yet the mechanisms enabling a privileged relationship with commensals remain largely unknown. Skin colonization by commensal Staphylococcus epidermidis facilitates immune tolerance preferentially in neonates via induction of antigen-specific regulatory T cells (Tregs). Here, we demonstrate that this tolerance is not indiscriminately extended to all bacteria encountered in this early window. Rather, neonatal colonization by Staphylococcus aureus minimally enriches for antigen-specific Tregs and does not prevent skin inflammation upon later-life exposure. S. aureus α-toxin contributes to this response by stimulating myeloid cell production of IL-1β, which limits S. aureus-specific Tregs. Loss of α-toxin or the IL-1 receptor increases Treg enrichment, whereas topical application of IL-1β or α-toxin diminishes tolerogenic responses to S. epidermidis. Thus, the preferential activation of a key alarmin pathway facilitates early discrimination of microbial "foe" from "friend," thereby preventing tolerance to a common skin pathogen.

Candida auris and Candida albicans can result in invasive fungal diseases. And yet, these species can stably and asymptomatically colonize human skin and gastrointestinal tracts. To consider these disparate microbial lifestyles, we first review factors shown to influence the underlying microbiome. Structured by the damage response framework, we then consider the molecular mechanisms deployed by C. albicans to switch between commensal and pathogenic lifestyles. Next, we explore this framework with C. auris to highlight how host physiology, immunity, and/or antibiotic receipt are associated with progression from colonization to infection. While treatment with antibiotics increases the risk that an individual will succumb to invasive candidiasis, the underlying mechanisms remain unclear. Here, we describe several hypotheses that may explain this phenomenon. We conclude by highlighting future directions integrating genomics with immunology to advance our understanding of invasive candidiasis and human fungal disease. In this review, Proctor and colleagues spotlight two fungal pathogens— Candida auris and Candida albicans —named by the World Health Organization as urgent health threats. They explore the role of the microbiome, host physiology, host immunity, and antibiotics in modulating switches between commensalism, pathogenesis, and infection in Candida species. [ABSTRACT FROM AUTHOR]