Functional roles of microbial cell-to-cell heterogeneity and emerging technologies for analysis and control.
Abstract Clonal cell populations often display significant cell-to-cell phenotypic heterogeneity, even when maintained under constant external conditions. This variability can result from the inherently stochastic nature of transcription and translation processes, which leads to varying numbers of transcripts and proteins per cell. Here, we showcase studies that reveal links between stochastic cellular events and biological functions in isogenic microbial populations. Then, we highlight emerging tools from engineering, computation, and synthetic and molecular biology that enable precise measurement, control, and a...
Source: Current Opinion in Microbiology - September 9, 2020 Category: Microbiology Authors: Sampaio NMV, Dunlop MJ Tags: Curr Opin Microbiol Source Type: research

Bacterial signaling as an antimicrobial target.
Abstract Antibiotics profoundly reduced worldwide mortality. However, the emergence of resistance to the growth inhibiting effects of these drugs occurred. New approaches to treat infectious disease that reduce the likelihood for resistance are needed. In bacterial pathogens, complex signaling networks regulate virulence. Anti-virulence therapies aim to disrupt these networks to attenuate virulence without affecting growth. Quorum-sensing, a cell-to-cell communication system, represents an attractive anti-virulence target because it often activates virulence. The challenge is to identify druggable targets that inh...
Source: Current Opinion in Microbiology - September 8, 2020 Category: Microbiology Authors: Ellermann M, Sperandio V Tags: Curr Opin Microbiol Source Type: research

Sensing the threat posed by Aspergillus infection.
Abstract The mammalian immune system can tune its inflammatory response to the threat level posed by an invading pathogen. It is well established that the host utilizes numerous 'patterns of pathogenicity', such as microbial growth, invasion, and viability, to achieve this tuning during bacterial infections. This review discusses how this notion fits during fungal infection, particularly regarding Aspergillus fumigatus infection. Moreover, how the environmental niches filled by A. fumigatus may drive the evolution of the fungal traits responsible for inducing the strain-specific inflammatory responses that have be...
Source: Current Opinion in Microbiology - September 5, 2020 Category: Microbiology Authors: Obar JJ Tags: Curr Opin Microbiol Source Type: research

Immunoglobulin A and the microbiome.
Abstract The trillions of microbes that constitutively colonize the intestine (the gut microbiota) impact diverse aspects of human physiology in health and disease. Immunoglobulin A (IgA) is the most abundant antibody isotype produced at mucosal surfaces, and nearly two grams of IgA is secreted into the intestine every day. Secretory IgA (SIgA) provides critical protection against pathogens and toxins, but can also directly bind to and 'coat' commensal bacteria in the gut. Commensal targeting by SIgA shapes gut microbiota composition, modulates bacterial behaviors, and enforces host-microbiota homeostasis in both ...
Source: Current Opinion in Microbiology - September 1, 2020 Category: Microbiology Authors: Yang Y, Palm NW Tags: Curr Opin Microbiol Source Type: research

Impact of bacterial persisters on their host.
Abstract The rise of antibiotic failure poses a severe threat to global health. There is growing concern that this failure is not solely driven by stable antibiotic resistance but also by a subpopulation of transiently non-growing, antibiotic tolerant bacteria. These 'persisters' have been proposed to seed relapsing infections, an important clinical outcome of treatment failure - although definitive evidence for this direct link remains elusive. Recent advances in the field have revealed the complex nature of intra-host persisters which drive their high adaptability through biosynthetic activity. These features of...
Source: Current Opinion in Microbiology - August 28, 2020 Category: Microbiology Authors: Moldoveanu AL, Rycroft JA, Helaine S Tags: Curr Opin Microbiol Source Type: research

Molecular mechanisms employed by enteric bacterial pathogens to antagonise host innate immunity.
Abstract Many Gram-negative enteric pathogens, including enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC), Salmonella, Shigella, and Yersinia species have evolved strategies to combat host defence mechanisms. Critical bacterial virulence factors, which often include but are not limited to type III secreted effector proteins, are deployed to cooperatively interfere with key host defence pathways. Recent studies in this area have not only contributed to our knowledge of bacterial pathogenesis, but have also shed light on the host pathways that are critical for controlling bacterial infection. ...
Source: Current Opinion in Microbiology - August 27, 2020 Category: Microbiology Authors: Gan J, Giogha C, Hartland EL Tags: Curr Opin Microbiol Source Type: research

Regulation of protein biosynthetic activity during growth arrest.
Abstract Heterotrophic bacteria grow and divide rapidly when resources are abundant. Yet resources are finite, and environments fluctuate, so bacteria need strategies to survive when nutrients become scarce. In fact, many bacteria spend most of their time in such conditions of nutrient limitation, and hence they need to optimise gene regulation and protein biosynthesis during growth arrest. An optimal strategy in these conditions must mitigate the challenges and risks of making new proteins, while the cell is severely limited for energy and substrates. Recently, ribosome abundance and activity were measured in the...
Source: Current Opinion in Microbiology - August 25, 2020 Category: Microbiology Authors: Bergkessel M Tags: Curr Opin Microbiol Source Type: research

CRISPR screens in the era of microbiomes.
Abstract Recent advances in genomics have uncovered the tremendous diversity and richness of microbial ecosystems. New functional genomics methods are now needed to probe gene function in high-throughput and provide mechanistic insights. Here, we review how the CRISPR toolbox can be used to inactivate, repress or overexpress genes in a sequence-specific manner and how this offers diverse attractive solutions to identify gene function in high-throughput. Developed both in eukaryotes and prokaryotes, CRISPR screening technologies have already provided meaningful insights in microbiology and host-pathogen interaction...
Source: Current Opinion in Microbiology - August 25, 2020 Category: Microbiology Authors: Rousset F, Bikard D Tags: Curr Opin Microbiol Source Type: research

Innate responses to gut microbiota; critical assessment of the necessary experimental controls.
Abstract The intestinal microbiota is comprises a diverse community of micro-organisms that interact with many host processes. Innate immune responses to the gut microbiota are of particular importance as they influence many other downstream responses. This fascinating host-microbe crosstalk is a rapidly expanding field of study; thus, it is critical to ensure reproducibility between studies and applicability to human clinical trials through standardization of experiments. We discuss here recent advances in the field including the spectrum of colonization statuses available, the critical importance of colonization...
Source: Current Opinion in Microbiology - August 23, 2020 Category: Microbiology Authors: McCoy KD, Ohland CL Tags: Curr Opin Microbiol Source Type: research

Kin recognition and outer membrane exchange (OME) in myxobacteria.
Abstract Myxobacteria conduct complex social traits that requires populations to be highly related and devoid of exploiters. To enrich for clonal cells in populations, they employ kin discrimination mechanisms. One key system involves a polymorphic cell surface receptor, TraA, which recognizes self by homotypic interactions with neighboring myxobacterial cells. Recent studies revealed that TraA and its partner TraB are fluid outer membrane proteins that coalesce into foci upon recognition of kin. The formation of foci leads to transient membrane fusion junctions and the bidirectional exchange of outer membrane com...
Source: Current Opinion in Microbiology - August 20, 2020 Category: Microbiology Authors: Sah GP, Wall D Tags: Curr Opin Microbiol Source Type: research

It's all in your head: antifungal immunity in the brain.
Abstract As the incidence rate of invasive fungal infections has increased with the use of modern medical interventions, so too has the occurrence of fungi invading the brain. Fungi such as Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus often infect immunocompromised individuals, and can use several strategies to invade the central nervous system (CNS) by penetrating the blood-brain barrier. Once in the brain parenchyma the specialized resident immune cells need to effectively recognize the fungus and mount an appropriate immune response to clear the infection, without causing debilitating im...
Source: Current Opinion in Microbiology - August 20, 2020 Category: Microbiology Authors: Snarr BD, Drummond RA, Lionakis MS Tags: Curr Opin Microbiol Source Type: research

PANoptosis in microbial infection.
Abstract The immune system has evolved multiple mechanisms to restrict microbial infections and regulate inflammatory responses. Without appropriate regulation, infection-induced inflammatory pathology can be deadly. The innate immune system recognizes the microbial molecules conserved in many pathogens and engages a rapid response by producing inflammatory mediators and activating programmed cell death pathways, including pyroptosis, apoptosis, and necroptosis. Activation of pattern recognition receptors, in combination with inflammatory cytokine-induced signaling through death domain-containing receptors, initia...
Source: Current Opinion in Microbiology - August 20, 2020 Category: Microbiology Authors: Place DE, Lee S, Kanneganti TD Tags: Curr Opin Microbiol Source Type: research

The antiviral activities of TRIM proteins.
Abstract Tripartite motif (TRIM) proteins are a highly versatile family of host-cell factors that play an integral role in the mammalian defense against pathogens. TRIM proteins regulate either transcription-dependent antiviral responses such as pro-inflammatory cytokine induction, or they modulate other important cell-intrinsic defense pathways like autophagy. Additionally, TRIM proteins exert direct antiviral activity whereby they antagonize specific viral components through diverse mechanisms. Here, we summarize the latest discoveries on the molecular mechanisms of antiviral TRIM proteins and also discuss curre...
Source: Current Opinion in Microbiology - August 20, 2020 Category: Microbiology Authors: Koepke L, Gack MU, Sparrer KM Tags: Curr Opin Microbiol Source Type: research

Engineered bacteria to report gut function: technologies and implementation.
Abstract Advances in synthetic biology and microbiology have enabled the creation of engineered bacteria which can sense and report on intracellular and extracellular signals. When deployed in vivo these whole-cell bacterial biosensors can act as sentinels to monitor biomolecules of interest in human health and disease settings. This is particularly interesting in the context of the gut microbiota, which interacts extensively with the human host throughout time and transit of the gut and can be accessed from feces without requiring invasive collection. Leveraging rational engineering approaches for genetic circuit...
Source: Current Opinion in Microbiology - August 19, 2020 Category: Microbiology Authors: Tanna T, Ramachanderan R, Platt RJ Tags: Curr Opin Microbiol Source Type: research

Single-cell reporters for pathogen responses to antimicrobial host attacks.
We present different types of reporters and their experimental advantages and challenges, and describe how different strategies can interrogate exposure to antimicrobial host mechanism, pathogen response, inflicted damage, and impact on pathogen fitness at the single-cell level. We find many gaps in available tools but also exciting avenues to address these issues. PMID: 32810800 [PubMed - as supplied by publisher] (Source: Current Opinion in Microbiology)
Source: Current Opinion in Microbiology - August 15, 2020 Category: Microbiology Authors: Roche B, Bumann D Tags: Curr Opin Microbiol Source Type: research

Hepatitis E virus: host tropism and zoonotic infection.
Abstract Hepatitis E virus (HEV), the causative agent of hepatitis E, is an understudied but important pathogen. HEV typically causes self-limiting acute viral hepatitis, however chronic infection with neurological and other extrahepatic manifestations has increasingly become a significant clinical problem. The discovery of swine HEV from pigs and demonstration of its zoonotic potential led to the genetic identification of very diverse HEV strains from more than a dozen other animal species. HEV strains from pig, rabbit, deer, camel, and rat have been shown to cross species barriers and infect humans. Zoonotic HEV...
Source: Current Opinion in Microbiology - August 15, 2020 Category: Microbiology Authors: Wang B, Meng XJ Tags: Curr Opin Microbiol Source Type: research

Shigella infection and host cell death: a double-edged sword for the host and pathogen survival.
Abstract In response to bacterial infection, epithelial cells undergo several types of cell death, including apoptosis, necrosis, pyroptosis, and necroptosis, which serve to expel the infected cells and activate the innate and acquired immune responses. Shigella initially invades macrophages and subsequently surrounding enterocytes; the pathogen executes macrophage cell death but prevents epithelial cell death in order to maintain its foothold for replication. To this end, Shigella delivers versatile effector proteins via the type III secretion system (T3SS), allowing it to efficiently colonize the intestinal epit...
Source: Current Opinion in Microbiology - August 9, 2020 Category: Microbiology Authors: Ashida H, Suzuki T, Sasakawa C Tags: Curr Opin Microbiol Source Type: research

Bacterial invasion and killing by predatory Bdellovibrio primed by predator prey cell recognition and self protection.
Abstract Bacterial predation, as exemplified by the periplasm-invading model predator Bdellovibrio bacteriovorus, is a fascinating multistage process facilitated by several adaptations to 'regular' bacterial lifestyles. We are beginning to understand more about such adaptations at the molecular level, particularly those concerning processes near the beginning of the predatory lifecycle (recognition, invasion, prey cell wall manipulation). In this review we highlight recent advances in investigating predation and tie these into some of the classical observations and phenotypes that make this two-cell system such an...
Source: Current Opinion in Microbiology - August 9, 2020 Category: Microbiology Authors: Caulton SG, Lovering AL Tags: Curr Opin Microbiol Source Type: research

Immunometabolism in fungal infections: the need to eat to compete.
Abstract Immune cells, including macrophages and monocytes, remodel their metabolism and have specific nutritional needs when dealing with microbial pathogens. While we are just beginning to understand immunometabolism in fungal infections, emerging themes include recognition of fungal cell surface molecule driving metabolic remodelling to increase glycolysis, the critical role of glycolysis in the production of antifungal cytokines and fungicidal effector molecules, and the need for maintaining host glucose homeostasis to defeat fungal infections. A crosstalk between host and pathogen metabolic pathways determine...
Source: Current Opinion in Microbiology - August 8, 2020 Category: Microbiology Authors: Weerasinghe H, Traven A Tags: Curr Opin Microbiol Source Type: research

An overview of the global antimicrobial resistance research and development hub and the current landscape.
Abstract Antimicrobial resistance (AMR) is an urgent public health threat, and continues to be on the rise. Basic microbiological research is the foundation for addressing knowledge gaps both for the development of new antibiotics, diagnostics and preventives but also to inform strategies to mitigate the transmission of resistance and drug resistant microorganisms. Translating this research into new products to reinvigorate dwindling pipelines, especially for new antibiotics, is one of the main challenges faced in addressing AMR. The scientific complexity is compounded by the market uncertainty of any new products...
Source: Current Opinion in Microbiology - August 7, 2020 Category: Microbiology Authors: Mattar C, Edwards S, Baraldi E, Hood J Tags: Curr Opin Microbiol Source Type: research

The antimalarial resistome - finding new drug targets and their modes of action.
Abstract To this day, malaria remains a global burden, affecting millions of people, especially those in sub-Saharan Africa and Asia. The rise of drug resistance to current antimalarial treatments, including artemisinin-based combination therapies, has made discovering new small molecule compounds with novel modes of action an urgent matter. The concerted effort to construct enormous compound libraries and develop high-throughput phenotypic screening assays to find compounds effective at specifically clearing malaria-causing Plasmodium parasites at any stage of the life cycle has provided many antimalarial prospec...
Source: Current Opinion in Microbiology - July 15, 2020 Category: Microbiology Authors: Carolino K, Winzeler EA Tags: Curr Opin Microbiol Source Type: research

Anti-fungal T cell responses in the lung and modulation by the gut-lung axis.
Abstract The lung is a central organ for immune-environmental interactions ranging from tolerance against harmless substances to protection against pathogens, which are particularly sensitive to regulation by the intestinal microbiota. Airborne fungi, can cause variety of diseases, including allergies and inflammatory disorders, as well as life-threatening invasive infections. Remarkable differences exist between ubiquitous fungal species with regard to protective immune mechanisms. Recent data have surprisingly identified Aspergillus-specific regulatory T cells as an essential tolerance checkpoint and provided me...
Source: Current Opinion in Microbiology - July 14, 2020 Category: Microbiology Authors: Scheffold A, Bacher P Tags: Curr Opin Microbiol Source Type: research

Blood type and the microbiome- untangling a complex relationship with lessons from pathogens.
Abstract The complex communities of microbes that constitute the human microbiome are influenced by host and environmental factors. Here, we address how a fundamental aspect of human biology, blood type, contributes to shaping this microscopic ecosystem. Although this question remains largely unexplored, we glean insights from decades of work describing relationships between pathogens and blood type. The bacterial strategies, molecular mechanisms, and host responses that shaped those relationships may parallel those that characterize how blood type and commensals interact. Understanding these nuanced interactions ...
Source: Current Opinion in Microbiology - July 11, 2020 Category: Microbiology Authors: Arnolds KL, Martin CG, Lozupone CA Tags: Curr Opin Microbiol Source Type: research

Probing the diversity and regulation of tRNA modifications.
Abstract Transfer RNAs (tRNAs) are non-coding RNAs essential for protein synthesis. tRNAs are heavily decorated with a variety of post-transcriptional modifications (tRNA modifications). Recent methodological advances provide new tools for rapid profiling of tRNA modifications and have led to discoveries of novel modifications and their regulation. Here, we provide an overview of the techniques for investigating tRNA modifications and of the expanding knowledge of their chemistry and regulation. PMID: 32663792 [PubMed - as supplied by publisher] (Source: Current Opinion in Microbiology)
Source: Current Opinion in Microbiology - July 11, 2020 Category: Microbiology Authors: Kimura S, Srisuknimit V, Waldor MK Tags: Curr Opin Microbiol Source Type: research

The bidirectional nature of microbiome-epithelial cell interactions.
Abstract The biogeography of the mammalian intestine is remarkable in that a vast microbial consortium exists inside the organism, surrounded by intestinal epithelial cells. The microbiome and the intestinal epithelium have developed a complex network of interactions that maintain intestinal homeostasis. We now recognize that functions of the epithelium are compartmentalized in specific intestinal epithelial cell subtypes. Furthermore, we are beginning to understand the ways in which microbes and their metabolic products impact the specific epithelial subsets. Here, we survey the mechanisms utilized by the microbi...
Source: Current Opinion in Microbiology - July 9, 2020 Category: Microbiology Authors: Solis AG, Klapholz M, Zhao J, Levy M Tags: Curr Opin Microbiol Source Type: research

Beyond the CRISPR-Cas safeguard: PICI-encoded innate immune systems protect bacteria from bacteriophage predation.
;s JR Abstract Phage satellites are genetic elements that depend on helper phages for induction, packaging and transfer. To promote their lifestyles, they have evolved elegant and sophisticated strategies to inhibit phage reproduction, which will be reviewed here. We will principally focus on the convergent interference mechanisms used by phage-inducible chromosomal islands (PICIs), which are a family of satellite phages present in both Gram-positive and Gram-negative bacteria. While some PICI elements have been extensively studied for their roles in virulence and antibiotic resistance, recent studies have highlig...
Source: Current Opinion in Microbiology - July 9, 2020 Category: Microbiology Authors: Fillol-Salom A, Miguel-Romero L, Marina A, Chen J, Penadés JR Tags: Curr Opin Microbiol Source Type: research

Molecular mechanisms of enterococcal-bacteriophage interactions and implications for human health.
Abstract Once overlooked as passive bystanders of the human intestinal microbiota, new evidence is shedding light on the importance of enterococci and their bacteriophages (phages) in shaping human health. Natural predators of enterococci, phages represent a narrow spectrum, precision targeting modality for the eradication of problematic enterococci within the microbiota or infected tissue. The identification of enterococcal phage receptors, absorption factors, and transcriptional responses following phage infection reveals a complex predator-prey relationship that modulates enterococcal cell surface architecture,...
Source: Current Opinion in Microbiology - July 8, 2020 Category: Microbiology Authors: Canfield GS, Duerkop BA Tags: Curr Opin Microbiol Source Type: research

Neonatal gut microbiome and immunity.
Abstract Early life is a critical time window for the neonatal gut to be progressively populated with different bacterial species that collectively promote gut maturation. A fully developed and healthy gut microbiome in neonates is an important driver for the development of other aspects of health. Unlike the relatively stable gut microbiome in adults, the developing gut microbiome in neonates exhibits higher plasticity and adaptability. This also underscores the unique window of opportunity for intervention or preventive measures to improve long-term health through modulations of the gut microbiome in early life....
Source: Current Opinion in Microbiology - July 4, 2020 Category: Microbiology Authors: Sanidad KZ, Zeng MY Tags: Curr Opin Microbiol Source Type: research

Perspectives in lung microbiome research.
Abstract Our understanding of the existence and role of the lung microbiome has grown at a slower pace than other microbiome research areas. This is likely a consequence of the original dogma that the lung was a sterile environment although there are other barriers that are worth discussing. Here we will not be conducting an exhaustive review of the current literature on the lung microbiome, but rather we will focus on what we see as some important challenges that the field needs to face in order to improve our mechanistic understanding of the lung microbiome and its role on human health. PMID: 32623064 [PubM...
Source: Current Opinion in Microbiology - July 2, 2020 Category: Microbiology Authors: Sulaiman I, Schuster S, Segal LN Tags: Curr Opin Microbiol Source Type: research

How antibiotics work together: molecular mechanisms behind combination therapy.
Abstract Antibiotics used in combination are an effective strategy for combatting numerous infectious diseases in clinical and veterinary settings, particularly as a last-line therapy for difficult-to-treat cases. Combination therapy can either increase or slow the rate of killing, broaden the antibiotic spectrum, reduce dosage and unwanted side-effects, and even control the emergence of resistance. The administration of antibiotics in combination has been used effectively against bacterial infections for>70 years, first used to treat tuberculosis. However, effective antibiotic combinations and their dosage reg...
Source: Current Opinion in Microbiology - June 30, 2020 Category: Microbiology Authors: Sullivan GJ, Delgado NN, Maharjan R, Cain AK Tags: Curr Opin Microbiol Source Type: research

Fecal transplants as a microbiome-based therapeutic.
Abstract Impaired microbiome diversity and composition can develop into a potent etiological agent of disease and increase susceptibility to infection. Given this, interventions targeting the microbiome have developed rapidly, with healthy donor feces being a de facto source of beneficial communities employed to rebalance patients' microbiomes. Recent evidence has demonstrated that bacterial and viral richness, short chain fatty acid production, bile acid conversion as well as presence of bacterial and fungal pathobionts are associated with therapy efficacy; however, little is known of the influence of host factor...
Source: Current Opinion in Microbiology - June 29, 2020 Category: Microbiology Authors: Kaakoush NO Tags: Curr Opin Microbiol Source Type: research

Soluble mediators in anti-fungal immunity.
nda V Abstract Although soluble mediators of our innate immune system have a substantial impact on invading microbes, their role against fungal pathogens has been underexplored. Constituting the humoral immunity, soluble mediators comprise the complement system, collectins, acute-phase proteins, antibodies and antimicrobial peptides. These components can prevent fungal infection either by directly interacting with invading microbes, leading to their aggregation (microbistatic), destruction (microbicidal) or linking them to cellular immunity. The composition of soluble-mediator varies with human body-fluids, result...
Source: Current Opinion in Microbiology - June 27, 2020 Category: Microbiology Authors: Dellière S, Sze Wah Wong S, Aimanianda V Tags: Curr Opin Microbiol Source Type: research

The gut, the bad and the harmless: Candida albicans as a commensal and opportunistic pathogen in the intestine.
Abstract Candida albicans is a regular member of the intestinal microbiota in the majority of the human population. This underscores C. albicans' adaptation to life in the intestine without inducing competitive interactions with other microbes, or immune responses detrimental to its survival. However, specific conditions such as a dysbalanced microbiome, a suppression of the immune system, and an impaired intestinal barrier can predispose for invasive, mostly nosocomial, C. albicans infections. Colonization of the intestine and translocation through the intestinal barrier are fundamental aspects of the processes p...
Source: Current Opinion in Microbiology - June 27, 2020 Category: Microbiology Authors: Kumamoto CA, Gresnigt MS, Hube B Tags: Curr Opin Microbiol Source Type: research

I want to break free - macrophage strategies to recognize and kill Candida albicans, and fungal counter-strategies to escape.
Abstract Candida albicans is a major cause of fungal nosocomial infections. Host defense against disseminated infections caused by this yeast strongly relies on myeloid cells of the innate immune system. Recently, several breakthroughs have been made that significantly improved our understanding of the role of macrophages during candidiasis and how C. albicans and macrophages interact. Resident tissue macrophages and macrophages derived from monocytes that infiltrate infected tissues are essential for the initiation of the antifungal immune response, as well as elimination of C. albicans from the bloodstream and i...
Source: Current Opinion in Microbiology - June 26, 2020 Category: Microbiology Authors: Austermeier S, Kasper L, Westman J, Gresnigt MS Tags: Curr Opin Microbiol Source Type: research

Minority report: the intestinal mycobiota in systemic infections.
Abstract Compared to bacteria, fungi often exhibit a lower abundance and a higher temporal volatility in the intestinal microbiota. Analysis of fungi in the microbiota (mycobiota) faces technical limitations with tools that were originally developed for analyzing bacteria. Dysbiotic states of the intestinal mycobiota, often associated with disruption of the healthy bacterial microbiota, are characterized by overgrowth (domination) of specific fungal taxa and loss of diversity. Intestinal domination by Candida species has been shown to be a major source of Candida bloodstream infections. Fungal dysbiosis is also li...
Source: Current Opinion in Microbiology - June 26, 2020 Category: Microbiology Authors: Rolling T, Hohl TM, Zhai B Tags: Curr Opin Microbiol Source Type: research

Targeted mutagenesis of multiple chromosomal regions in microbes.
acute;l C Abstract Directed evolution allows the effective engineering of proteins, biosynthetic pathways, and cellular functions. Traditional plasmid-based methods generally subject one or occasionally multiple genes-of-interest to mutagenesis, require time-consuming manual interventions, and the genes that are subjected to mutagenesis are outside of their native genomic context. Other methods mutagenize the whole genome unselectively which may distort the outcome. Recent recombineering- and CRISPR-based technologies radically change this field by allowing exceedingly high mutation rates at multiple, predefined l...
Source: Current Opinion in Microbiology - June 26, 2020 Category: Microbiology Authors: Csörgő B, Nyerges A, Pál C Tags: Curr Opin Microbiol Source Type: research

Microbiome-mediated regulation of anti-fungal immunity.
Abstract Anti-fungal immunity is characterized by the continuous interplay between immune activation and immune regulation processes. These processes have now been clearly shown not only in animal pre-clinical models but also in humans. To create and maintain this immune homeostasis, reciprocal interactions among the host immune system, fungal pathogens, and the microbiome are crucial. Notably, the microbiome exerts multiple direct and indirect antifungal effects that are particularly aimed at minimizing host tissue damage. Thus, in this microbiome era, the architecture of 3D culture system or 'tissue organoids' m...
Source: Current Opinion in Microbiology - June 13, 2020 Category: Microbiology Authors: Zelante T, Costantini C, Romani L Tags: Curr Opin Microbiol Source Type: research

Who's in control? Regulation of metabolism and pathogenesis in space and time.
Abstract Bacterial pathogens need to sense and respond to their environments during infection to align cell metabolism and virulence factor production to survive and battle host defenses. Complex regulatory networks including ligand-binding transcription factors, two-component systems, RNA-binding proteins, and small non-coding regulatory RNAs adjust gene expression programs in response to changes in metabolic fluxes, environmental cues, and nutrient availability. Recent studies underlined that these different layers of regulation occur along varying spatial and temporal scales, leading to changes in cell behavior...
Source: Current Opinion in Microbiology - June 9, 2020 Category: Microbiology Authors: King AN, de Mets F, Brinsmade SR Tags: Curr Opin Microbiol Source Type: research

Mapping bacterial effector arsenals: in vivo and in silico approaches to defining the protein features dictating effector secretion by bacteria.
Abstract Many bacterial pathogens rely on dedicated secretion systems to translocate virulence proteins termed 'effectors' into host cells. These effectors engage and manipulate host cellular functions to support bacterial colonization and propagation. The secretion systems are molecular machines that recognize targeting 'features' in these effector proteins in vivo to selectively and efficiently secrete them. The joint analysis of whole genome sequencing data and computational predictions of amino acid characteristics of effector proteins has made available extensive lists of candidate effectors for many bacteria...
Source: Current Opinion in Microbiology - June 4, 2020 Category: Microbiology Authors: Lee YW, Wang J, Newton HJ, Lithgow T Tags: Curr Opin Microbiol Source Type: research

Systems biology of host-Candida interactions: understanding how we shape each other.
Abstract Candida albicans is both a member of the human mucosal microbiota and a common agent of invasive fungal disease. Systems biology approaches allow for analysis of the interactions between this fungus and its mammalian host. Framing these studies by considering how C. albicans and its host construct the niche the other occupies provides insight into how these interactions shape the ecosystems, behavior, and evolution of each organism. Here, we discuss recent work on multiscale systems biology approaches for examining C. albicans in relation to the host ecosystem to identify the emergent properties of the in...
Source: Current Opinion in Microbiology - May 30, 2020 Category: Microbiology Authors: Hodgins-Davis A, O'Meara TR Tags: Curr Opin Microbiol Source Type: research

Metabolic control of virulence factor production in Staphylococcus aureus.
Abstract As investigators decipher the underlining mechanisms of Staphylococcus aureus pathogenesis, it is becoming apparent that perturbations in central metabolism alter virulence factor production and infection outcomes. It is also evident that S. aureus has the ability to metabolically adapt to improve colonization and overcome challenges imparted by the immune system. Altered metabolite pools modify virulence factor production suggesting that proper functioning of a core metabolic network is necessary for successful niche colonization and pathogenesis. Herein we discuss four examples of transcriptional regula...
Source: Current Opinion in Microbiology - May 7, 2020 Category: Microbiology Authors: Rudra P, Boyd JM Tags: Curr Opin Microbiol Source Type: research

Regulatory networks important for survival of Acinetobacter baumannii within the host.
Abstract Acinetobacter baumannii is known for its intrinsic resistance to conventional antibiotic treatment and hypervirulence during infection. This coupled with its extraordinary capacity to survive in myriad harsh environments has led to increasing rates of infection in clinical settings. Numerous studies have characterized the virulence factors and resistance genes in A. baumannii responsible for the detrimental outcomes seen in patients; however, the role of regulatory factors in controlling the expression of these genes remains less well explored. Herein we discuss the latest and most influential findings on...
Source: Current Opinion in Microbiology - May 6, 2020 Category: Microbiology Authors: Allen JL, Tomlinson BR, Casella LG, Shaw LN Tags: Curr Opin Microbiol Source Type: research

The acid response network of Staphylococcus aureus.
Abstract Staphylococcus aureus colonizes or causes infection in a multitude of niches within a mammalian host. Many of these niches are acidic, yet specific pH resistance mechanisms that facilitate survival have not been thoroughly investigated. This review discusses recent studies documenting known acid resistance mechanisms in S. aureus and other staphylococcal species. However, studies that clearly define the regulation of the acid resistance regulon and potential interactions with weak organic acids in specific niches of the host including the skin and gut are yet to be defined. PMID: 32361405 [PubMed - a...
Source: Current Opinion in Microbiology - April 29, 2020 Category: Microbiology Authors: Zhou C, Fey PD Tags: Curr Opin Microbiol Source Type: research

Gastrointestinal host-pathogen interaction in the age of microbiome research.
AJ Abstract The microbiota is linked to human health by governing susceptibility to infection. However, the interplay between enteric pathogens, the host, and its microbiota is complex, encompassing host cell manipulation by virulence factors, immune responses, and a diverse gut ecosystem. The host represents a foundation species that uses its immune system as a habitat filter to shape the gut microbiota. In turn, the gut microbiota protects against ecosystem invasion by opportunistic pathogens through priority effects that are based on niche modification or niche preemption. Frank pathogens can overcome these pr...
Source: Current Opinion in Microbiology - April 25, 2020 Category: Microbiology Authors: Tsolis RM, Bäumler AJ Tags: Curr Opin Microbiol Source Type: research

Antifungal drug screening: thinking outside the box to identify novel antifungal scaffolds.
Abstract Invasive fungal infections are responsible for a significant disease burden worldwide. Drugs to treat these infections are limited to only four unique classes, and despite these available treatments, mortality rates remain unacceptably high. In this review, we will discuss antifungal drug screening and how the approach to identifying novel compounds needs move away from traditional growth-based assays in order to meet the demand for new drugs. We highlight specific examples of creative screening strategies that increase the likelihood of identifying compounds with desired activities and provide perspectiv...
Source: Current Opinion in Microbiology - April 24, 2020 Category: Microbiology Authors: Beattie SR, Krysan DJ Tags: Curr Opin Microbiol Source Type: research

Applying microbial ecology to antimicrobial discovery.
Abstract Introduction of antibiotics into clinical use has contributed to some of the greatest improvements to public health in the 20th century. Most antibiotics are based on antimicrobials that were isolated from environmental microorganisms over 50 years ago, but emerging resistance requires discovery of new molecules and development of these molecules into therapeutics. Bioinformatic analyses of microbial genomes indicate that many more microbial bioactive molecules remain undiscovered. Understanding when, where, and why these molecules are produced informs efforts to tap into the hidden unexplored chemical di...
Source: Current Opinion in Microbiology - April 24, 2020 Category: Microbiology Authors: Pishchany G Tags: Curr Opin Microbiol Source Type: research

Staphylococci in the human microbiome: the role of host and interbacterial interactions.
Abstract Staphylococci are common commensals on human epithelial surfaces. Some species, most notably Staphylococcus aureus, have considerable pathogenic potential and can cause severe and sometimes fatal infections. Despite the long-known fact that staphylococcal infection arises from colonizing isolates, research on staphylococcal colonization has been limited, in particular regarding interactions with the colonizing microbiota. However, several recent studies are beginning to decipher such interactions, which range from bacteriocin-based or signaling interference-mediated inhibitory interactions to cooperation ...
Source: Current Opinion in Microbiology - April 13, 2020 Category: Microbiology Authors: Otto M Tags: Curr Opin Microbiol Source Type: research

Comparative genomics in infectious disease.
Abstract With more than one million bacterial genome sequences uploaded to public databases in the last 25 years, genomics has become a powerful tool for studying bacterial biology. Here, we review recent approaches that leverage large numbers of whole genome sequences to decipher the spread and pathogenesis of bacterial infectious diseases. PMID: 32248056 [PubMed - as supplied by publisher] (Source: Current Opinion in Microbiology)
Source: Current Opinion in Microbiology - April 2, 2020 Category: Microbiology Authors: Moustafa AM, Lal A, Planet PJ Tags: Curr Opin Microbiol Source Type: research

Linking bacterial growth, survival, and multicellularity - small signaling molecules as triggers and drivers.
Abstract An overarching theme of cellular regulation in bacteria arises from the trade-off between growth and stress resilience. In addition, the formation of biofilms contributes to stress survival, since these dense multicellular aggregates, in which cells are embedded in an extracellular matrix of self-produced polymers, represent a self-constructed protective and homeostatic 'niche'. As shown here for the model bacterium Escherichia coli, the inverse coordination of bacterial growth with survival and the transition to multicellularity is achieved by a highly integrated regulatory network with several sigma sub...
Source: Current Opinion in Microbiology - March 31, 2020 Category: Microbiology Authors: Hengge R Tags: Curr Opin Microbiol Source Type: research

Quantitative modeling of the interplay between synthetic gene circuits and host physiology: experiments, results, and prospects.
rtínez-Antonio A Abstract A primary goal of synthetic biology is to develop gene circuits that perform their intended functions despite variations in the growth conditions. However, this has turned out to be more complicated than it originally seemed because there is a complex interplay between the operation of synthetic gene circuits and the global physiology of host cells. Mathematical models provide an avenue to disentangle the intricacies of this phenomenon and guide the design of synthetic circuits that robustly perform in a variety of conditions. In this work, we review quantitative modeling approache...
Source: Current Opinion in Microbiology - March 25, 2020 Category: Microbiology Authors: Sánchez-Osorio I, Hernández-Martínez CA, Martínez-Antonio A Tags: Curr Opin Microbiol Source Type: research