Annual review of microbiology最新文献

During the essential processes of DNA replication and transcription, RNA-DNA hybrid intermediates are formed that pose significant risks to genome integrity when left unresolved. To manage RNA-DNA hybrids, all cells rely on RNase H family enzymes that specifically cleave the RNA portion of the many different types of hybrids that form in vivo. Recent experimental advances have provided new insight into how RNA-DNA hybrids form and the consequences to genome integrity that ensue when persistent hybrids remain unresolved. Here we review the types of RNA-DNA hybrids, including R-loops, RNA primers, and ribonucleotide misincorporations, that form during DNA replication and transcription and discuss how each type of hybrid can contribute to genome instability in bacteria. Further, we discuss how bacterial RNase HI, HII, and HIII and bacterial FEN enzymes contribute to genome maintenance through the resolution of hybrids.

Invasive fungal infections are emerging diseases that kill over 1.5 million people per year worldwide. With the increase of immunocompromised populations, the incidence of invasive fungal infections is expected to continue to rise. Vaccines for viral and bacterial infectious diseases have had a transformative impact on human health worldwide. However, no fungal vaccines are currently in clinical use. Recently, interest in fungal vaccines has grown significantly. One Candida vaccine has completed phase 2 clinical trials, and research on vaccines against coccidioidomycosis continues to advance. Additionally, multiple groups have discovered various Cryptococcus mutant strains that promote protective responses to subsequent challenge in mouse models. There has also been progress in antibody-mediated fungal vaccines. In this review, we highlight recent fungal vaccine research progress, outline the wealth of data generated, and summarize current research for both fungal biology and immunology studies relevant to fungal vaccine development. We also review technological advancements in vaccine development and highlight the future prospects of a human vaccine against invasive fungal infections.

Antibiotic resistance is a serious public health concern, and new drugs are needed to ensure effective treatment of many bacterial infections. Bacterial type II fatty acid synthesis (FASII) is a vital aspect of bacterial physiology, not only for the formation of membranes but also to produce intermediates used in vitamin production. Nature has evolved a repertoire of antibiotics inhibiting different aspects of FASII, validating these enzymes as potential targets for new antibiotic discovery and development. However, significant obstacles have been encountered in the development of FASII antibiotics, and few FASII drugs have advanced beyond the discovery stage. Most bacteria are capable of assimilating exogenous fatty acids. In some cases they can dispense with FASII if fatty acids are present in the environment, making the prospects for identifying broad-spectrum drugs against FASII targets unlikely. Single-target, pathogen-specific FASII drugs appear the best option, but a major drawback to this approach is the rapid acquisition of resistance via target missense mutations. This complication can be mitigated during drug development by optimizing the compound design to reduce the potential impact of on-target missense mutations at an early stage in antibiotic discovery. The lessons learned from the difficulties in FASII drug discovery that have come to light over the last decade suggest that a refocused approach to designing FASII inhibitors has the potential to add to our arsenal of weapons to combat resistance to existing antibiotics.

Since Jacques Monod's foundational work in the 1940s, investigators studying bacterial physiology have largely (but not exclusively) focused on the exponential phase of bacterial cultures, which is characterized by rapid growth and high biosynthesis activity in the presence of excess nutrients. However, this is not the predominant state of bacterial life. In nature, most bacteria experience nutrient limitation most of the time. In fact, investigators even prior to Monod had identified other aspects of bacterial growth, including what is now known as the stationary phase, when nutrients become limiting. This review will discuss how bacteria transition to growth arrest in response to nutrient limitation through changes in transcription, translation, and metabolism. We will then examine how these changes facilitate survival during potentially extended periods of nutrient limitation, with particular attention to the metabolic strategies that underpin bacterial longevity in this state.

Bacteria orchestrate collective behaviors and accomplish feats that would be unsuccessful if carried out by a lone bacterium. Processes undertaken by groups of bacteria include bioluminescence, biofilm formation, virulence factor production, and release of public goods that are shared by the community. Collective behaviors are controlled by signal transduction networks that integrate sensory information and transduce the information internally. Here, we discuss network features and mechanisms that, even in the face of dramatically changing environments, drive precise execution of bacterial group behaviors. We focus on representative quorum-sensing and second-messenger cyclic dimeric GMP (c-di-GMP) signal relays. We highlight ligand specificity versus sensitivity, how small-molecule ligands drive discrimination of kin versus nonkin, signal integration mechanisms, single-input sensory systems versus coincidence detectors, and tuning of input-output dynamics via feedback regulation. We summarize how different features of signal transduction systems allow groups of bacteria to successfully interpret and collectively react to dynamically changing environments.

The longstanding interactions between mammals and their symbionts enable thousands of mammal species to consume herbivorous diets. The microbial communities in mammals degrade both plant fiber and toxins. Microbial toxin degradation has been repeatedly documented in domestic ruminants, but similar work in wild mammals is more limited due to constraints on sampling and manipulating the microbial communities in these species. In this review, we briefly describe the toxins commonly encountered in mammalian diets, major classes of biotransformation enzymes in microbes and mammals, and the gut chambers that house symbiotic microbes. We next examine evidence for microbial detoxification in domestic ruminants before providing case studies on microbial toxin degradation in both foregut- and hindgut-fermenting wild mammals. We end by discussing species that may be promising for future investigations, and the advantages and limitations of approaches currently available for studying degradation of toxins by mammalian gut microbes.

Although microbes are routinely grown in monocultures in the laboratory, they are almost never encountered as single species in the wild. Our ability to detect and identify new microorganisms has advanced significantly in recent years, but our understanding of the mechanisms that mediate microbial interactions has lagged behind. What makes this task more challenging is that microbial alliances can be dynamic, consisting of multiple phases. The transitions between phases, and the interactions in general, are often mediated by a chemical language consisting of small molecules, also referred to as secondary metabolites or natural products. In this microbial lexicon, the molecules are like words and through their effects on recipient cells they convey meaning. The current review highlights three dynamic microbial interactions in which some of the words and their meanings have been characterized, especially those that mediate transitions in selected multiphasic associations. These systems provide insights into the principles that govern microbial symbioses and a playbook for interrogating similar associations in diverse ecological niches.

The malaria parasite life cycle alternates between two hosts: a vertebrate and the female Anopheles mosquito vector. Cell division, proliferation, and invasion are essential for parasite development, transmission, and survival. Most research has focused on Plasmodium development in the vertebrate, which causes disease; however, knowledge of malaria parasite development in the mosquito (the sexual and transmission stages) is now rapidly accumulating, gathered largely through investigation of the rodent malaria model, with Plasmodium berghei. In this review, we discuss the seminal genome-wide screens that have uncovered key regulators of cell proliferation, invasion, and transmission during Plasmodium sexual development. Our focus is on the roles of transcription factors, reversible protein phosphorylation, and molecular motors. We also emphasize the still-unanswered important questions around key pathways in cell division during the vector transmission stages and how they may be targeted in future studies.