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issn:0966-842
1.  Porphyromonas gingivalis neutrophil manipulation: risk factor for Periodontitis? 
Trends in microbiology  2014;22(8):428-429.
Defining the contribution of individual members of dysbiotic host associated bacterial communities has been difficult. The recent paper by Maekawa et al. in Cell host Microbe describes bacterial manipulation of neutrophil responses by Porphyromonas gingivalis as a mechanism that contributes to forming a dysbiotic community.
doi:10.1016/j.tim.2014.06.006
PMCID: PMC4132835  PMID: 25001854
2.  Is selection relevant in the evolutionary emergence of drug resistance? 
Trends in microbiology  2015;23(3):126-133.
The emergence of drug resistant pathogens is often considered a canonical case of evolution by ‘natural’ selection. Here we argue that the strength of selection can be a poor predictor of the rate of resistance emergence. It is possible for a resistant strain to be under negative selection and still emerge in an infection or spread in a population. Measuring the right parameters is a necessary first step towards the development of evidence-based resistance management strategies. We argue that it is the absolute fitness of the resistant strains that matters most, and that a primary determinant of the absolute fitness of a resistant strain when it arises is the ecological context in which it finds itself.
doi:10.1016/j.tim.2015.01.005
PMCID: PMC4494118  PMID: 25680587
Evolutionary rescue; chemotherapy; antibiotics; mutant selection window
3.  Clostridium difficile spore biology: sporulation, germination, and spore structural proteins 
Trends in microbiology  2014;22(7):406-416.
Clostridium difficile is a Gram-positive, spore-forming obligate anaerobe and a major nosocomial pathogen of world-wide concern. Due to its strict anaerobic requirements, the infectious and transmissible morphotype is the dormant spore. In susceptible patients, C. difficile spores germinate in the colon to form the vegetative cells that initiate Clostridium difficile infections (CDI). During CDI, C. difficile induces a sporulation pathway that produces more spores; these spores are responsible for the persistence of C. difficile in patients and horizontal transmission between hospitalized patients. While important to the C. difficile lifecycle, the C. difficile spore proteome is poorly conserved when compared to members of the Bacillus genus. Further, recent studies have revealed significant differences between C. difficile and B. subtilis at the level of sporulation, germination and spore coat and exosporium morphogenesis. In this review, the regulation of the sporulation and germination pathways and the morphogenesis of the spore coat and exosporium will be discussed.
doi:10.1016/j.tim.2014.04.003
PMCID: PMC4098856  PMID: 24814671
C. difficile spores; sporulation; germination; spore coat; exosporium
4.  Listeria exploits damage and death to spread bad news 
Trends in microbiology  2014;22(7):370-371.
Pathogenic Listeria monocytogenes replicates within the host cytosol; little is known about how it transits from cell to cell, spreading infection. A recent study implicates infection-induced membrane damage as a trigger for efferocytosis, the recognition and uptake of dead cells, thereby tricking neighboring cells into taking up the invader.
doi:10.1016/j.tim.2014.06.001
PMCID: PMC4116131  PMID: 24934861
Listeria; dissemination; efferocytosis; membrane damage
5.  The role of matrix in HIV-1 envelope glycoprotein incorporation 
Trends in microbiology  2014;22(7):372-378.
Incorporation of the viral envelope (Env) glycoprotein is a critical requirement for the production of infectious HIV-1 particles. It has long been appreciated that the matrix (MA) domain of the Gag polyprotein and the cytoplasmic tail of Env are central players in the process of Env incorporation, but the precise mechanisms have been elusive. A number of recent developments have thrown light on the contributions of both proteins, prompting a re-evaluation of the role of MA during Env incorporation. The two domains appear to play distinct but complementary roles, with the cytoplasmic tail of Env responsible for directing Env to the site of assembly and the matrix domain accommodating the cytoplasmic tail of Env in the Gag lattice.
doi:10.1016/j.tim.2014.04.012
PMCID: PMC4157688  PMID: 24933691
HIV-1; matrix; envelope; assembly; packaging
6.  Anthrax lethal and edema toxins in anthrax pathogenesis 
Trends in microbiology  2014;22(6):317-325.
The pathophysiological effects resulting from many bacterial diseases are caused by exotoxins released by the bacteria. Bacillus anthracis, a spore-forming bacterium, is such a pathogen, causing anthrax through a combination of bacterial infection and toxemia. B. anthracis causes natural infection in humans and animals and has been a top bioterrorism concern since the 2001 anthrax attacks in the USA. The exotoxins secreted by B. anthracis use CMG2 as the major toxin receptor and play essential roles in pathogenesis during the entire course of the disease. This review focuses on the activities of anthrax toxins and their roles in initial and late stages of anthrax infection.
doi:10.1016/j.tim.2014.02.012
PMCID: PMC4041834  PMID: 24684968
Anthrax; Capillary morphogenesis protein 2; edema toxin; lethal toxin; Tumor endothelial marker 8
7.  Chaperone fusion proteins aid entropy-driven maturation of class II viral fusion proteins 
Trends in microbiology  2013;22(2):100-106.
Class II viral fusion proteins are present on the envelope of flaviviruses and togaviruses, viruses that often cause tropical and subtropical diseases. These proteins use a second membrane protein as a molecular chaperone to assist their folding and to ensure proper function during viral assembly, maturation, and infection. Recent progress in structural studies of dengue viruses has revealed how the chaperone pre-membrane (prM) protein guides viral maturation and how pH is sensed in both the maturation and infection processes. Drastic conformation changes and reorganization of these viral membrane proteins occur during the transition from their metastable to stable structural states in a unidirectional, entropy-driven process.
doi:10.1016/j.tim.2013.11.006
PMCID: PMC4445943  PMID: 24380727
cryo-electron microscopy; flavivirus; togavirus; bio-threat agent; enveloped viruses; structures
8.  Functional and phylogenetic assembly of microbial communities in the human microbiome 
Trends in microbiology  2014;22(5):261-266.
doi:10.1016/j.tim.2014.01.011
PMCID: PMC4008634  PMID: 24618403
human microbiome; microbial ecology; metagenomics; functional ecology
9.  Omics approaches in food safety: fulfilling the promise? 
Trends in microbiology  2014;22(5):275-281.
Genomics, transcriptomics, and proteomics are rapidly transforming our approaches to detection, prevention and treatment of foodborne pathogens. Microbial genome sequencing in particular has evolved from a research tool into an approach that can be used to characterize foodborne pathogen isolates as part of routine surveillance systems. Genome sequencing efforts will not only improve outbreak detection and source tracking, but will also create large amounts of foodborne pathogen genome sequence data, which will be available for data mining efforts that could facilitate better source attribution and provide new insights into foodborne pathogen biology and transmission. While practical uses and application of metagenomics, transcriptomics, and proteomics data and associated tools are less prominent, these tools are also starting to yield practical food safety solutions.
doi:10.1016/j.tim.2014.01.006
PMCID: PMC4016976  PMID: 24572764
Genomics; transcriptomics; proteomics; synthetic biology; foodborne pathogens; food safety
10.  Ordering microbial diversity into ecologically and genetically cohesive units 
Trends in microbiology  2014;22(5):235-247.
We propose that microbial diversity must be viewed in light of gene flow and selection, which define units of genetic similarity, and of phenotype and ecological function, respectively. Here, we discuss to what extent ecological and genetic units overlap to form cohesive populations in the wild, based on recent evolutionary modeling and on evidence from some of the first microbial populations studied with genomics. These show that if recombination is frequent and selection moderate, ecologically adaptive mutations or genes can spread within populations independently of their original genomic background (gene-specific sweeps). Alternatively, if the effect of recombination is smaller than selection, genome-wide selective sweeps should occur. In both cases, however, distinct units of overlapping ecological and genotypic similarity will form if microgeographic separation, likely involving ecological tradeoffs, induces barriers to gene flow. These predictions are supported by (meta)genomic data, which suggest that a ‘reverse ecology’ approach, in which genomic and gene flow information is used to make predictions about the nature of ecological units, is a powerful approach to ordering microbial diversity.
doi:10.1016/j.tim.2014.02.006
PMCID: PMC4103024  PMID: 24630527
population genomics; ecological differentiation; reverse ecology; gene flow; selective sweeps; mosaic sympatric speciation
11.  A novel membrane fusion protein family in Flaviviridae? 
Trends in microbiology  2014;22(4):176-182.
Enveloped viruses must fuse their lipid membrane to a cellular membrane to deliver their genome into the cytoplasm for replication. Viral envelope proteins catalyze this critical membrane fusion event. They fall into three distinct structural classes. In 2013, envelope proteins from a pestivirus and hepatitis C virus were found to have two distinct novel folds. This was unexpected because these viruses are in the same family as flaviviruses, which have class II fusion proteins. We propose that the membrane fusion machinery of the closely related pestiviruses and hepatitis C virus defines a new structural class. This and other recently identified structural relationships between viral fusion proteins shift the paradigm for how these proteins evolved.
doi:10.1016/j.tim.2014.01.008
PMCID: PMC3985287  PMID: 24569295
Bovine viral diarrhea virus; hepacivirus; host-virus coevolution; horizontal gene transfer; envelope glycoprotein; paleovirology
12.  GSK3β and the control of infectious bacterial diseases 
Trends in microbiology  2014;22(4):208-217.
Glycogen synthesis kinase 3β (GSK3β) has been shown to be a critical mediator of the intensity and direction of the innate immune system responding to bacterial stimuli. This review will focus on: (i) the central role of GSK3β in the regulation of pathogen-induced inflammatory responses through the regulation of pro- and anti-inflammatory cytokine production. (ii) The extensive ongoing efforts to exploit GSK3β for its therapeutic potential in the control of infectious diseases. (iii) The increasing evidence that specific pathogens target GSK3β-related pathways for immune evasion. A better understanding of complex bacterial–GSK3β interactions is likely to lead to more effective anti-inflammatory interventions and novel targets to circumvent pathogen colonization and survival.
doi:10.1016/j.tim.2014.01.009
PMCID: PMC4003878  PMID: 24618402
GSK3β; cytokines; immune evasion; inflammation; septic shock; TLRs
13.  Different Paths to Pathogenesis 
Trends in microbiology  2014;22(4):168-169.
In a recent issue of Cell Host & Microbe, Elsen and colleagues identify a novel hemolysin in a highly virulent Pseudomonas aeruginosa strain that lacks a type 3 secretion system. Their analysis provides another example of how individual strains of P. aeruginosa utilize different virulence mechanisms to cause severe infections.
doi:10.1016/j.tim.2014.02.013
PMCID: PMC4027030  PMID: 24629347
14.  Long-lived reservoirs of HIV-1 
Trends in microbiology  2014;22(4):173-175.
HIV-1 persistence in long-lived cellular reservoirs remains a major barrier to a cure. In a recent Nature Medicine paper, Buzon et al. identify memory T cells with stem cell-like properties (TSCM) that harbor infectious provirus and that likely contribute to HIV-1 persistence.
doi:10.1016/j.tim.2014.02.015
PMCID: PMC4048589  PMID: 24641995
15.  Emerging roles of immunostimulatory oral bacteria in periodontitis development 
Trends in microbiology  2014;22(3):157-163.
Periodontitis is a common dental disease which results in irreversible alveolar bone loss around teeth, and subsequent tooth loss. Previous studies have focused on bacteria that damage the host and the roles of commensals to facilitate their colonization. Although some immune responses targeting oral bacteria protect the host from alveolar bone loss, recent studies show that particular host defense responses to oral bacteria can induce alveolar bone loss. Host damaging and immunostimulatory oral bacteria cooperatively induce bone loss by inducing gingival damage followed by immunostimulation. In mouse models of experimental periodontitis induced by either Porphyromonas gingivalis or ligature, γ-proteobacteria accumulate and stimulate host immune responses to induce host damage. Here we review the differential roles of individual bacterial groups in promoting bone loss through the induction of host damage and immunostimulation.
doi:10.1016/j.tim.2013.12.005
PMCID: PMC3943594  PMID: 24433922
periodontitis; NOD1; pathobiont; innate immunity; alveolar bone absorption; neutrophil recruitment
16.  [No title available] 
PMCID: PMC3918648  PMID: 24268716
17.  Combating enteropathogenic Escherichia coli (EPEC) infections: the way forward 
Trends in microbiology  2013;21(7):317-319.
Enteropathogenic Escherichia coli (EPEC) strains continue to cause severe and sometimes fatal infantile diarrhea, particularly in Africa. Increased efforts at diagnosis, defining the clinical spectrum of disease, understanding pathogenic mechanisms, and delineating immune responses are desperately needed to develop new strategies to combat EPEC.
doi:10.1016/j.tim.2013.05.003
PMCID: PMC4312613  PMID: 23815982
translational research; diarrhea; mortality; infants; immunity; vaccines
18.  Vesicular transport across the fungal cell wall 
Trends in microbiology  2009;17(4):158-162.
Recent findings indicate that fungi use vesicular transport to deliver substances across their cell walls. Fungal vesicles are similar to mammalian exosomes and could originate from cytoplasmic multivesicular bodies. Vesicular transport enables the export of large molecules across the cell wall, and vesicles contain lipids, proteins and polysaccharides, many of which are associated with virulence. Concentration of fungal products in vesicles could increase their efficiency in food acquisition and/or delivering potentially noxious substances to other cells, such as amoebae or phagocytes. The discovery of vesicular transport in fungi opens many new avenues for investigation in basic cell biology and pathogenesis.
doi:10.1016/j.tim.2008.12.005
PMCID: PMC4282776  PMID: 19299133
19.  Cell targeting by the Staphylococcus aureus pore-forming toxins: It’s not just about lipids 
Trends in microbiology  2013;22(1):21-27.
Staphylococcus aureus employs numerous pore-forming cytotoxins to injure host immune cells and promote infection. Until recently, it was unclear how these cytotoxins targeted specific cell types for lysis. Membrane lipids were initially postulated to be cytotoxin receptor candidates. However, the cell-type specificity and species-dependent targeting of these toxins did not support lipids as sole receptors. The recent identification of proteinaceous receptors for several S. aureus cytotoxins now provides an explanation for the observed tropism. These findings also have important implications for the implementation of animal models to study S. aureus pathogenesis, and for the development of novel therapeutics.
doi:10.1016/j.tim.2013.10.004
PMCID: PMC3929396  PMID: 24231517
Pore-forming toxins; toxin receptors; membrane proteins Staphylococcus aureus
20.  PIP2: choreographer of actin-adaptor proteins in the HIV-1 dance 
Trends in microbiology  2014;22(7):379-388.
The actin cytoskeleton plays a key role during the replication cycle of human immunodeficiency virus-1 (HIV-1). HIV-1 infection is affected by cellular proteins that influence the clustering of viral receptors or the subcortical actin cytoskeleton. Several of these actin-adaptor proteins are controlled by the second messenger phosphatidylinositol 4,5-biphosphate (PIP2), an important regulator of actin organization. PIP2 production is induced by HIV-1 attachment and facilitates viral infection. However, the importance of PIP2 in regulating cytoskeletal proteins and thus HIV-1 infection has been overlooked. This review examines recent reports describing the roles played by actin-adaptor proteins during HIV-1 infection of CD4+ T cells, highlighting the influence of the signaling lipid PIP2 in this process.
doi:10.1016/j.tim.2014.03.009
PMCID: PMC4171680  PMID: 24768560
PIP2; actin-binding proteins; HIV-1
21.  Chemosensory Signaling Systems That Control Bacterial Survival 
Trends in microbiology  2014;22(7):389-398.
Recent studies have revealed that several Gram-negative species utilize variations of the well-known chemotaxis signaling cascade to switch lifestyles in order to survive environmental stress. Two survival strategies covered in this review are the development of dormant cyst cells and biofilm formation. Both of these two types of structures involve exopolysaccharide-mediated cell-cell interactions which result in multicellular communities that confer resistance to stress conditions such as desiccation and antibiotics. This review is centered on recent advances in the understanding of phosphate flow and novel output signals in chemosensory signaling pathways that are involved in cyst formation and biofilms.
doi:10.1016/j.tim.2014.04.004
PMCID: PMC4273944  PMID: 24794732
Chemotaxis-Like; Signal; Transduction; Systems
22.  Decoding the complexity of type I interferon to treat persistent viral infections 
Trends in microbiology  2013;21(12):10.1016/j.tim.2013.10.003.
Type I interferons (IFN-I) are a broad family of cytokines that are central to the innate immune response. These proteins have long been appreciated for the critical roles they play in restraining viral infections and shaping antiviral immune responses. However, in recent years there has been increased awareness of the immunosuppressive actions of these proteins as well. While there are many current therapeutic applications to manipulate IFN-I pathways we have limited understanding of the mechanisms by which these therapies are actually functioning. In this review we highlight the diversity and temporal impact of IFN-I signaling, discuss the current therapeutic uses of IFN-I, and explore the strategy of blocking IFN-I to alleviate immune dysfunction in persistent virus infections.
doi:10.1016/j.tim.2013.10.003
PMCID: PMC3864553  PMID: 24216022
type I interferon; persistent; virus; LCMV; immunosuppression; therapy; immune activation; HIV
23.  Bacterial lifestyle shapes the regulation of stringent response activation 
Trends in microbiology  2013;21(4):174-180.
Bacteria inhabit enormously diverse niches and have a correspondingly large array of regulatory mechanisms to adapt to often inhospitable and variable environments. The stringent response allows bacteria to quickly reprogram transcription in response to changes in nutrient availability. Although the proteins controlling this response are conserved in almost all bacterial species, recent work has illuminated considerable diversity in the starvation cues and regulatory mechanisms that activate stringent signaling proteins in bacteria from different environments. In this review we describe the signals and genetic circuitries that control the stringent signaling systems of a copiotroph, a bacteriovore, an oligotroph and a mammalian pathogen – Escherichia coli, Myxococcus xanthus, Caulobacter crescentus and Mycobacterium tuberculosis, respectively – and discuss how control of the stringent response in these species is adapted to their particular lifestyles.
doi:10.1016/j.tim.2013.01.002
PMCID: PMC4238387  PMID: 23419217
stringent response; niche; ppGpp; RelA; SpoT; stress response
24.  Rising to the challenge: new therapies for tuberculosis 
Trends in microbiology  2013;21(9):493-501.
Standard treatment for tuberculosis (TB) is lengthy, complex and significantly toxic. Drug development for TB has stagnated for decades; but in recent years renewed commitment and coordinated research has generated a modest pipeline of new drugs that hold the potential to make treatment more effective, shorter, less complex and less toxic in the near future. With a particular focus on bedaquiline (TMC207), the first antituberculosis drug of a novel class to be FDA-approved in 40 years, this review summarizes the recent evidence behind new developments in tuberculosis treatment. Novel drug classes, repurposed drugs and host-directed therapies are reviewed. In parallel to these exciting developments in drug-discovery, we propose that it is crucial to develop more rapid and comprehensive diagnostics that will allow for the timely selection of the best regimen for individual patients.
doi:10.1016/j.tim.2013.05.002
PMCID: PMC4237170  PMID: 23764389
Tuberculosis; Bedaquiline; PA-824; Delamanid; Clofazimine; Oxazolidinones
25.  Unexpected structure of Epstein–Barr virus lytic cycle activator Zta 
Trends in microbiology  2006;14(7):289-291.
The key viral gene responsible for initiating the replicative cycle of Epstein–Barr virus (EBV), termed BZLF1, encodes the multifunctional protein Zta (ZEBRA or Z). It interacts with DNA as both a transcription and a replication factor, modulates both intracellular signal transduction and the DNA-damage response and manipulates cell cycle progression. Muller and colleagues have resolved the structure of Zta bound to DNA, which confirms some structural predictions but reveals an unexpected twist and a complex dimerization interface. Because EBV is associated with human disease, Zta presents a prime target for drug design.
doi:10.1016/j.tim.2006.05.003
PMCID: PMC4221735  PMID: 16730442

Results 1-25 (155)