bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of Attenuation of Uranyl Toxicity by Glutathione in Lactococcus lactis
Authors: Obeid Muhammad H. , Oertel Jana , Solioz Marc , Fahmy Karim 
Published: April 2016

ABSTRACT

Both prokaryotic and eukaryotic organisms possess mechanisms for the detoxification of heavy metals, and these mechanisms are found among distantly related species. We investigated the role of intracellular glutathione (GSH), which, in a large number of taxa, plays a role in protection against the toxicity of common heavy metals. Anaerobically grown
Lactococcus lactis
containing an inducible GSH synthesis pathway was used as a model organism. Its physiological condition allowed study of putative GSH-dependent uranyl detoxification mechanisms without interference from additional reactive oxygen species. By microcalorimetric measurements of metabolic heat during cultivation, it was shown that intracellular GSH attenuates the toxicity of uranium at a concentration in the range of 10 to 150 μM. In this concentration range, no effect was observed with copper, which was used as a reference for redox metal toxicity. At higher copper concentrations, GSH aggravated metal toxicity. Isothermal titration calorimetry revealed the endothermic binding of U(VI) to the carboxyl group(s) of GSH rather than to the reducing thiol group involved in copper interactions. The data indicate that the primary detoxifying mechanism is the intracellular sequestration of carboxyl-coordinated U(VI) into an insoluble complex with GSH. The opposite effects on uranyl and on copper toxicity can be related to the difference in coordination chemistry of the respective metal-GSH complexes, which cause distinct growth phase-specific effects on enzyme-metal interactions.

IMPORTANCE
Understanding microbial metal resistance is of particular importance for bioremediation, where microorganisms are employed for the removal of heavy metals from the environment. This strategy is increasingly being considered for uranium. However, little is known about the molecular mechanisms of uranyl detoxification. Existing studies of different taxa show little systematics but hint at a role of glutathione (GSH). Previous work could not unequivocally demonstrate a GSH function in decreasing the presumed uranyl-induced oxidative stress, nor could a redox-independent detoxifying action of GSH be identified. Combining metabolic calorimetry with cell number-based assays and genetics analysis enables a novel and general approach to quantify toxicity and relate it to molecular mechanisms. The results show that GSH-expressing microorganisms appear advantageous for uranyl bioremediation.
Cationized Magnetoferritin Enables Rapid Labeling and Concentration of Gram-Positive and Gram-Negative Bacteria in Magnetic Cell Separation Columns
Authors: Correia Carreira S. , Spencer J. , Schwarzacher W. , Seddon A. M. 
Published: April 2016

ABSTRACT

In order to identify pathogens rapidly and reliably, bacterial capture and concentration from large sample volumes into smaller ones are often required. Magnetic labeling and capture of bacteria using a magnetic field hold great promise for achieving this goal, but the current protocols have poor capture efficiency. Here, we present a rapid and highly efficient approach to magnetic labeling and capture of both Gram-negative (
Escherichia coli
) and Gram-positive (
Staphylococcus aureus
) bacteria using cationized magnetoferritin (cat-MF). Magnetic labeling was achieved within a 1-min incubation period with cat-MF, and 99.97% of the labeled bacteria were immobilized in commercially available magnetic cell separation (MACS) columns. Longer incubation times led to more efficient capture, with
S. aureus
being immobilized to a greater extent than
E. coli
. Finally, low numbers of magnetically labeled
E. coli
bacteria (<100 CFU per ml) were immobilized with 100% efficiency and concentrated 7-fold within 15 min. Therefore, our study provides a novel protocol for rapid and highly efficient magnetic labeling, capture, and concentration of both Gram-positive and Gram-negative bacteria.

IMPORTANCE
Antimicrobial resistance (AMR) is a significant global challenge. Rapid identification of pathogens will retard the spread of AMR by enabling targeted treatment with suitable agents and by reducing inappropriate antimicrobial use. Rapid detection methods based on microfluidic devices require that bacteria are concentrated from large volumes into much smaller ones. Concentration of bacteria is also important to detect low numbers of pathogens with confidence. Here, we demonstrate that magnetic separation columns capture small amounts of bacteria with 100% efficiency. Rapid magnetization was achieved by exposing bacteria to cationic magnetic nanoparticles, and magnetized bacteria were concentrated 7-fold inside the column. Thus, bacterial capture and concentration were achieved within 15 min. This approach could be extended to encompass the capture and concentration of specific pathogens, for example, by functionalizing magnetic nanoparticles with antibodies or small molecule probes.
The Role of Punctuated Evolution in the Pathogenicity of Influenza Viruses
Authors: McCullers Jonathan A. 
Published: April 2016

ABSTRACT
Influenza is an acute respiratory disease caused by influenza viruses. Evolutionarily, all influenza viruses are zoonoses, arising in the animal reservoir and spilling over into the human population. Several times a century, one of these zoonotic events results in a new influenza virus lineage becoming established in humans and circulating for years or decades as an endemic strain. The worldwide pandemic that occurs shortly after the nascent virus becomes established can have a profound impact on morbidity and mortality. Because influenza viruses continually evolve and the illness they engender can vary considerably based on characteristics of the strain, the weather, other circulating or endemic pathogens, as well as the number of susceptible hosts, the impact of each season on human health is unpredictable. Over time, the general pattern is for pandemic strains to adapt and gradually take on characteristics of seasonal strains with lower virulence and a diminished synergism with bacterial pathogens. Study of this punctuated evolution yields a number of insights into the overall pathogenicity of influenza viruses.
Bacterial Prostatitis: Bacterial Virulence, Clinical Outcomes, and New Directions
Authors: Krieger John N. , Thumbikat Praveen 
Published: April 2016

ABSTRACT

Four prostatitis syndromes are recognized clinically: acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis/chronic pelvic pain syndrome, and asymptomatic prostatitis. Because
Escherichia coli
represents the most common cause of bacterial prostatitis, we investigated the importance of bacterial virulence factors and antimicrobial resistance in
E. coli
strains causing prostatitis and the potential association of these characteristics with clinical outcomes. A structured literature review revealed that we have limited understanding of the virulence-associated characteristics of
E. coli
causing acute prostatitis. Therefore, we completed a comprehensive microbiological and molecular investigation of a unique strain collection isolated from healthy young men. We also considered new data from an animal model system suggesting certain
E. coli
might prove important in the etiology of chronic prostatitis/chronic pelvic pain syndrome. Our human data suggest that
E. coli
needs multiple pathogenicity-associated traits to overcome anatomic and immune responses in healthy young men without urological risk factors. The phylogenetic background and accumulation of an exceptional repertoire of extraintestinal pathogenic virulence-associated genes indicate that these
E. coli
strains belong to a highly virulent subset of uropathogenic variants. In contrast, antibiotic resistance confers little added advantage to
E. coli
strains in these healthy outpatients. Our animal model data also suggest that certain pathogenic
E. coli
may be important in the etiology of chronic prostatitis/chronic pelvic pain syndrome through mechanisms that are dependent on the host genetic background and the virulence of the bacterial strain.
Gram-Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract
Authors: Kline Kimberly A. , Lewis Amanda L. 
Published: April 2016

ABSTRACT

Gram-positive bacteria are a common cause of urinary-tract infection (UTI), particularly among individuals who are elderly, pregnant, or who have other risk factors for UTI. Here we review the epidemiology, virulence mechanisms, and host response to the most frequently isolated Gram-positive uropathogens:
Staphylococcus saprophyticus, Enterococcus faecalis
, and
Streptococcus agalactiae
. We also review several emerging, rare, misclassified, and otherwise underreported Gram-positive pathogens of the urinary tract including
Aerococcus
,
Corynebacterium, Actinobaculum,
and
Gardnerella
. The literature strongly suggests that urologic diseases involving Gram-positive bacteria may be easily overlooked due to limited culture-based assays typically utilized for urine in hospital microbiology laboratories. Some UTIs are polymicrobial in nature, often involving one or more Gram-positive bacteria. We herein review the risk factors and recent evidence for mechanisms of bacterial synergy in experimental models of polymicrobial UTI. Recent experimental data has demonstrated that, despite being cleared quickly from the bladder, some Gram-positive bacteria can impact pathogenic outcomes of co-infecting organisms. When taken together, the available evidence argues that Gram-positive bacteria are important uropathogens in their own right, but that some can be easily overlooked because they are missed by routine diagnostic methods. Finally, a growing body of evidence demonstrates that a surprising variety of fastidious Gram-positive bacteria may either reside in or be regularly exposed to the urinary tract and further suggests that their presence is widespread among women, as well as men. Experimental studies in this area are needed; however, there is a growing appreciation that the composition of bacteria found in the bladder could be a potentially important determinant in urologic disease, including susceptibility to UTI.
Drug and Vaccine Development for the Treatment and Prevention of Urinary Tract Infections
Authors: O’Brien Valerie P. , Hannan Thomas J. , Nielsen Hailyn V. , Hultgren Scott J. 
Published: April 2016

ABSTRACTUrinary tract infections (UTI) are among the most common bacterial infections in humans, affecting millions of people every year. UTI cause significant morbidity in women throughout their lifespan, in infant boys, in older men, in individuals with underlying urinary tract abnormalities, and in those that require long-term urethral catheterization, such as patients with spinal cord injuries or incapacitated individuals living in nursing homes. Serious sequelae include frequent recurrences, pyelonephritis with sepsis, renal damage in young children, pre-term birth, and complications of frequent antimicrobial use including high-level antibiotic resistance andClostridium difficilecolitis. UropathogenicE. coli(UPEC) cause the vast majority of UTI, but less common pathogens such asEnterococcus faecalisand other enterococci frequently take advantage of an abnormal or catheterized urinary tract to cause opportunistic infections. While antibiotic therapy has historically been very successful in controlling UTI, the high rate of recurrence remains a major problem, and many individuals suffer from chronically recurring UTI, requiring long-term prophylactic antibiotic regimens to prevent recurrent UTI. Furthermore, the global emergence of multi-drug resistant UPEC in the past ten years spotlights the need for alternative therapeutic and preventative strategies to combat UTI, including anti-infective drug therapies and vaccines. In this chapter, we review recent advances in the field of UTI pathogenesis, with an emphasis on the identification of promising drug and vaccine targets. We then discuss the development of new UTI drugs and vaccines, highlighting the challenges these approaches face and the need for a greater understanding of urinary tract mucosal immunity.
The Structure and Function of Type III Secretion Systems
Authors: Notti Ryan Q. , Stebbins C. Erec 
Published: April 2016

ABSTRACT
Type III secretion systems (T3SSs) afford Gram-negative bacteria an intimate means of altering the biology of their eukaryotic hosts—the direct delivery of effector proteins from the bacterial cytoplasm to that of the eukaryote. This incredible biophysical feat is accomplished by nanosyringe “injectisomes,” which form a conduit across the three plasma membranes, peptidoglycan layer, and extracellular space that form a barrier to the direct delivery of proteins from bacterium to host. The focus of this chapter is T3SS function at the structural level; we will summarize the core findings that have shaped our understanding of the structure and function of these systems and highlight recent developments in the field. In turn, we describe the T3SS secretory apparatus, consider its engagement with secretion substrates, and discuss the posttranslational regulation of secretory function. Lastly, we close with a discussion of the future prospects for the interrogation of structure-function relationships in the T3SS.
Bacterial Evasion of Host Antimicrobial Peptide Defenses
Authors: Cole Jason N. , Nizet Victor 
Published: April 2016

ABSTRACT
Antimicrobial peptides (AMPs), also known as host defense peptides, are small naturally occurring microbicidal molecules produced by the host innate immune response that function as a first line of defense to kill pathogenic microorganisms by inducing deleterious cell membrane damage. AMPs also possess signaling and chemoattractant activities and can modulate the innate immune response to enhance protective immunity or suppress inflammation. Human pathogens have evolved defense molecules and strategies to counter and survive the AMPs released by host immune cells such as neutrophils and macrophages. Here, we review the various mechanisms used by human bacterial pathogens to resist AMP-mediated killing, including surface charge modification, active efflux, alteration of membrane fluidity, inactivation by proteolytic digestion, and entrapment by surface proteins and polysaccharides. Enhanced understanding of AMP resistance at the molecular level may offer insight into the mechanisms of bacterial pathogenesis and augment the discovery of novel therapeutic targets and drug design for the treatment of recalcitrant multidrug-resistant bacterial infections.

Abbreviations: ABC, adenosine triphosphate-binding cassette; AMPs, antimicrobial peptides;
l
-Ara4N, 4-amino-4-deoxy-
l
-arabinose; GAC, group A carbohydrate; GAS, group A
Streptococcus
; GBS, group B
Streptococcus
; GlcNAc,
N
-acetylglucosamine; HBD 1-6, human β-defensin 1-6; HD 5-6, human α-defensin 5-6; HNP 1-4, human neutrophil peptide 1-4; LL-37, human cathelicidin; LOS, lipooligosaccharide; LPS, lipopolysaccharide; LTA, lipoteichoic acid; mCRAMP, murine cathelicidin-related antimicrobial peptide; MprF, membrane protein multipeptide resistance factor; NETs, neutrophil extracellular traps; pEtN, phosphoethanolamine; PG, phosphatidylglycerol; Sap, sensitive to antimicrobial peptides ABC importer; SK, staphylokinase; TA, teichoic acid; TLR, toll-like receptor; WT, wild-type.
Type VII Secretion: A Highly Versatile Secretion System
Authors: Ates Louis S. , Houben Edith N. G. , Bitter Wilbert 
Published: April 2016

ABSTRACTType VII secretion (T7S) systems of mycobacteria secrete substrates over the unusual diderm cell envelope. Furthermore, T7S gene clusters are present throughout the phylumActinobacteria, and functional T7S-like systems have been identified inFirmicutes. Most of the T7S substrates can be divided into two families: the Esx proteins, which are found in bothFirmicutesandActinobacteria, and the PE and PPE proteins, which are more mycobacterium-specific. Members of both families have been shown to be secreted as folded heterodimers, suggesting that this is a conserved feature of T7S substrates. Most knowledge of the mechanism of T7S and the roles of T7S systems in virulence comes from studies of pathogenic mycobacteria. These bacteria can contain up to five T7S systems, called ESX-1 to ESX-5, each having its own role in bacterial physiology and virulence.In this article, we discuss the general composition of T7S systems and the role of the individual components in secretion. These conserved components include two membrane proteins with (predicted) enzymatic activities: a predicted ATPase (EccC), likely to be required for energy provision of T7S, and a subtilisin-like protease (MycP) involved in processing of specific substrates. Additionally, we describe the role of a conserved intracellular chaperone in T7S substrate recognition, based on recently published crystal structures and molecular analysis. Finally, we discuss system-specific features of the different T7S systems in mycobacteria and their role in pathogenesis and provide an overview of the role of T7S in virulence of other pathogenic bacteria.
Bacterial Secretion Systems: An Overview
Authors: Green Erin R. , Mecsas Joan 
Published: April 2016

ABSTRACT
Bacterial pathogens utilize a multitude of methods to invade mammalian hosts, damage tissue sites, and thwart the immune system from responding. One essential component of these strategies for many bacterial pathogens is the secretion of proteins across phospholipid membranes. Secreted proteins can play many roles in promoting bacterial virulence, from enhancing attachment to eukaryotic cells, to scavenging resources in an environmental niche, to directly intoxicating target cells and disrupting their functions. Many pathogens use dedicated protein secretion systems to secrete virulence factors from the cytosol of the bacteria into host cells or the host environment. In general, bacterial protein secretion apparatuses can be divided into classes, based on their structures, functions, and specificity. Some systems are conserved in all classes of bacteria and secrete a broad array of substrates, while others are only found in a small number of bacterial species and/or are specific to only one or a few proteins. In this chapter, we review the canonical features of several common bacterial protein secretion systems, as well as their roles in promoting the virulence of bacterial pathogens. Additionally, we address recent findings that indicate that the innate immune system of the host can detect and respond to the presence of protein secretion systems during mammalian infection.
Novel Targets of Antimicrobial Therapies
Authors: Maddocks Sarah E. 
Published: April 2016

ABSTRACT
Antibiotics are undoubtedly a pillar of modern medicine; their discovery in 1929 revolutionized the fight against infectious disease, instigating a worldwide decline in infection-associated mortality. Throughout the 1930s, 1940s, and 1950s the golden age of antibiotic discovery was underway with numerous new classes of antibiotics identified and brought to market. By 1962 all of our currently known families of antibiotics had been discovered, and it was a widely held belief, that humanity had conquered infectious disease. Despite varying bacterial cellular targets, most antibiotics targeted exponentially multiplying bacteria by interfering with integral processes such as peptidoglycan synthesis or ribosomal activity. The very nature of this targeted approach has driven the emergence of antibiotic-resistant bacteria.
Methods of antibiotic identification relied solely on scientific observation, and while chemical analogues such as amoxicillin, derived from penicillin, continued to be developed, they retained the same mechanisms of action and hence the same bacterial targets. This article describes and discusses some of the emerging novel targets for antimicrobial treatments, highlighting pivotal research on which our ability to continue to successfully treat bacterial infection relies.
Innovative Solutions to Sticky Situations: Antiadhesive Strategies for Treating Bacterial Infections
Authors: Cusumano Zachary T. , Klein Roger D. , Hultgren Scott J. 
Published: April 2016

ABSTRACT
Bacterial adherence to host tissue is an essential process in pathogenesis, necessary for invasion and colonization and often required for the efficient delivery of toxins and other bacterial effectors. As existing treatment options for common bacterial infections dwindle, we find ourselves rapidly approaching a tipping point in our confrontation with antibiotic-resistant strains and in desperate need of new treatment options. Bacterial strains defective in adherence are typically avirulent and unable to cause infection in animal models. The importance of this initial binding event in the pathogenic cascade highlights its potential as a novel therapeutic target. This article seeks to highlight a variety of strategies being employed to treat and prevent infection by targeting the mechanisms of bacterial adhesion. Advancements in this area include the development of novel antivirulence therapies using small molecules, vaccines, and peptides to target a variety of bacterial infections. These therapies target bacterial adhesion through a number of mechanisms, including inhibition of pathogen receptor biogenesis, competition-based strategies with receptor and adhesin analogs, and the inhibition of binding through neutralizing antibodies. While this article is not an exhaustive description of every advancement in the field, we hope it will highlight several promising examples of the therapeutic potential of antiadhesive strategies.
Prevalence of passive smoking in the community population aged 15 years and older in China: a systematic review and meta-analysis
Authors: Zeng Jing , Yang Shanshan , Wu Lei , Wang Jianhua , Wang Yiyan , Liu Miao , Zhang Di , Jiang Bin , He Yao 
Published: April 2016

ObjectivesTo estimate the prevalence and distribution of passive smoking in the community population aged 15 years and older in China.DesignA systematic review and meta-analysis of cross-sectional studies reporting the prevalence of passive smoking in China and a series of subgroup, trend and sensitivity analyses were conducted in this study.Data sourceThe systematic review and meta-analysis, which included 46 studies with 381 580 non-smokers, estimated the prevalence and distribution of passive smoking in China. All studies were published between 1997 and 2015.ResultsThe pooled prevalence of passive smoking was 48.7% (95% CI 44.8% to 52.5%) and was relatively stable from 1995 to 2013. The prevalence in the subgroups of gender, area, age and time varied from 35.1% (95% CI 31.8% to 38.3%) in the elderly (≥60 years) to 48.6% (95% CI 42.9% to 54.2%) in urban areas. The prevalence was lower in the elderly (≥60 years) than in those between 15 and 59 years of age (OR 1.61, 95% CI 1.44 to 1.81). The difference between females and males in urban and rural areas was not statistically significant (OR: 1.27, 95% CI 0.93 to 1.74 and OR: 1.14, 95% CI 0.82 to 1.58, respectively). In addition, a significantly increasing trend was found among males from 2002 to 2010. Heterogeneity was high in all pooled estimates (I2>98%, p<0.001).ConclusionsThe high and stable prevalence of passive smoking in China is raising increasing national concern regarding specific research and tobacco control programmes. Attention should be focused on young, middle-aged and male non-smokers regardless of region.