Delayed Toxicity Associated with Soluble Anthrax Toxin Receptor Decoy-Ig Fusion Protein Treatment

Soluble receptor decoy inhibitors, including receptor-immunogloubulin (Ig) fusion proteins, have shown promise as candidate anthrax toxin therapeutics. These agents act by binding to the receptor-interaction site on the protective antigen (PA) toxin subunit, thereby blocking toxin binding to cell surface receptors. Here we have made the surprising observation that co-administration of receptor decoy-Ig fusion proteins significantly delayed, but did not protect, rats challenged with anthrax lethal toxin. The delayed toxicity was associated with the in vivo assembly of a long-lived complex comprised of anthrax lethal toxin and the receptor decoy-Ig inhibitor. Intoxication in this system presumably results from the slow dissociation of the toxin complex from the inhibitor following their prolonged circulation. We conclude that while receptor decoy-Ig proteins represent promising candidates for the early treatment of B. anthracis infection, they may not be suitable for therapeutic use at later stages when fatal levels of toxin have already accumulated in the bloodstream

Regulation of MntH by a Dual Mn(II)- and Fe(II)-Dependent Transcriptional Repressor (DR2539) in Deinococcus radiodurans

The high intracellular Mn/Fe ratio observed within the bacteria Deinococcus radiodurans may contribute to its remarkable resistance to environmental stresses. We isolated DR2539, a novel regulator of intracellular Mn/Fe homeostasis in D. radiodurans. Electrophoretic gel mobility shift assays (EMSAs) revealed that DR2539 binds specifically to the promoter of the manganese acquisition transporter (MntH) gene, and that DR0865, the only Fur homologue in D. radiodurans, cannot bind to the promoter of mntH, but it can bind to the promoter of another manganese acquisition transporter, MntABC. β-galactosidase expression analysis indicated that DR2539 acts as a manganese- and iron-dependent transcriptional repressor. Further sequence alignment analysis revealed that DR2539 has evolved some special characteristics. Site-directed mutagenesis suggested that His98 plays an important role in the activities of DR2539, and further protein-DNA binding activity assays showed that the activity of H98Y mutants decreased dramatically relative to wild type DR2539. Our study suggests that D. radiodurans has evolved a very efficient manganese regulation mechanism that involves its high intracellular Mn/Fe ratio and permits resistance to extreme conditions

Bacterial adaptation is constrained in complex communities

© 2020, The Author(s). A major unresolved question is how bacteria living in complex communities respond to environmental changes. In communities, biotic interactions may either facilitate or constrain evolution depending on whether the interactions expand or contract the range of ecological opportunities. A fundamental challenge is to understand how the surrounding biotic community modifies evolutionary trajectories as species adapt to novel environmental conditions. Here we show that community context can dramatically alter evolutionary dynamics using a novel approach that ‘cages’ individual focal strains within complex communities. We find that evolution of focal bacterial strains depends on properties both of the focal strain and of the surrounding community. In particular, there is a stronger evolutionary response in low-diversity communities, and when the focal species have a larger genome and are initially poorly adapted. We see how community context affects resource usage and detect genetic changes involved in carbon metabolism and inter-specific interaction. The findings demonstrate that adaptation to new environmental conditions should be investigated in the context of interspecific interactions

The Importance of Socio-Economic Versus Environmental Risk Factors for Reported Dengue Cases in Java, Indonesia

Background: Dengue is a major mosquito-borne viral disease and an important public health problem. Identifying which factors are important determinants in the risk of dengue infection is critical in supporting and guiding preventive measures. In South-East Asia, half of all reported fatal infections are recorded in Indonesia, yet little is known about the epidemiology of dengue in this country. Methodology/Principal findings: Hospital-reported dengue cases in Banyumas regency, Central Java were examined to build Bayesian spatial and spatio-temporal models assessing the influence of climatic, demographic and socio-economic factors on the risk of dengue infection. A socio-economic factor linking employment type and economic status was the most influential on the risk of dengue infection in the Regency. Other factors such as access to healthcare facilities and night-time temperature were also found to be associated with higher risk of reported dengue infection but had limited explanatory power. Conclusions/Significance: Our data suggest that dengue infections are triggered by indoor transmission events linked to socio-economic factors (employment type, economic status). Preventive measures in this area should therefore target also specific environments such as schools and work areas to attempt and reduce dengue burden in this community. Although our analysis did not account for factors such as variations in immunity which need further investigation, this study can advise preventive measures in areas with similar patterns of reported dengue cases and environmen

Factors associated with compliance among users of solar water disinfection in rural Bolivia

ABSTRACT: BACKGROUND: Diarrhoea is the second leading cause of childhood mortality, with an estimated 1.3 million deaths per year. Promotion of Solar Water Disinfection (SODIS) has been suggested as a strategy for reducing the global burden of diarrhoea by improving the microbiological quality of drinking water. Despite increasing support for the large-scale dissemination of SODIS, there are few reports describing the effectiveness of its implementation. It is, therefore, important to identify and understand the mechanisms that lead to adoption and regular use of SODIS. METHODS: We investigated the behaviours associated with SODIS adoption among households assigned to receive SODIS promotion during a cluster-randomized trial in rural Bolivia. Distinct groups of SODIS-users were identified on the basis of six compliance indicators using principal components and cluster analysis. The probability of adopting SODIS as a function of campaign exposure and household characteristics was evaluated using ordinal logistic regression models. RESULTS: Standardised, community-level SODIS-implementation in a rural Bolivian setting was associated with a median SODIS use of 32% (IQR: 17-50). Households that were more likely to use SODIS were those that participated more frequently in SODIS promotional events (OR = 1.07, 95%CI: 1.01-1.13), included women (OR = 1.18, 95%CI: 1.07-1.30), owned latrines (OR = 3.38, 95%CI: 1.07-10.70), and had severely wasted children living in the home (OR = 2.17, 95%CI: 1.34-3.49). CONCLUSIONS: Most of the observed household characteristics showed limited potential to predict compliance with a comprehensive, year-long SODIS-promotion campaign; this finding reflects the complexity of behaviour change in the context of household water treatment. However, our findings also suggest that the motivation to adopt new water treatment habits and to acquire new knowledge about drinking water treatment is associated with prior engagements in sanitary hygien and with the experience of contemporary family health concerns.Household-level factors like the ownership of a latrine, a large proportion of females and the presence of a malnourished child living in a home are easily assessable indicators that SODIS-programme managers could use to identify early adopters in SODIS promotion campaigns. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0073149

Parallel Evolution of a Type IV Secretion System in Radiating Lineages of the Host-Restricted Bacterial Pathogen Bartonella

Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biological diversity by exploiting an exceptional range of environments, yet diversification of bacteria via adaptive radiation has been documented in a few cases only and the underlying molecular mechanisms are largely unknown. Here we show a compelling example of adaptive radiation in pathogenic bacteria and reveal their genetic basis. Our evolutionary genomic analyses of the α-proteobacterial genus Bartonella uncover two parallel adaptive radiations within these host-restricted mammalian pathogens. We identify a horizontally-acquired protein secretion system, which has evolved to target specific bacterial effector proteins into host cells as the evolutionary key innovation triggering these parallel adaptive radiations. We show that the functional versatility and adaptive potential of the VirB type IV secretion system (T4SS), and thereby translocated Bartonella effector proteins (Beps), evolved in parallel in the two lineages prior to their radiations. Independent chromosomal fixation of the virB operon and consecutive rounds of lineage-specific bep gene duplications followed by their functional diversification characterize these parallel evolutionary trajectories. Whereas most Beps maintained their ancestral domain constitution, strikingly, a novel type of effector protein emerged convergently in both lineages. This resulted in similar arrays of host cell-targeted effector proteins in the two lineages of Bartonella as the basis of their independent radiation. The parallel molecular evolution of the VirB/Bep system displays a striking example of a key innovation involved in independent adaptive processes and the emergence of bacterial pathogens. Furthermore, our study highlights the remarkable evolvability of T4SSs and their effector proteins, explaining their broad application in bacterial interactions with the environment

Ecological and geographical overlap drive plumage evolution and mimicry in woodpeckers.

Organismal appearances are shaped by selection from both biotic and abiotic drivers. For example, Gloger's rule describes the pervasive pattern that more pigmented populations are found in more humid areas. However, species may also converge on nearly identical colours and patterns in sympatry, often to avoid predation by mimicking noxious species. Here we leverage a massive global citizen-science database to determine how biotic and abiotic factors act in concert to shape plumage in the world's 230 species of woodpeckers. We find that habitat and climate profoundly influence woodpecker plumage, and we recover support for the generality of Gloger's rule. However, many species exhibit remarkable convergence explained neither by these factors nor by shared ancestry. Instead, this convergence is associated with geographic overlap between species, suggesting occasional strong selection for interspecific mimicry

The environmental plasmid pQBR103 alters the single-cell Raman spectral profile of Pseudomonas fluorescens SBW25

Although plasmids are ubiquitous amongst phytosphere pseudomonads, the advantage and costs of plasmids for the bacterial host remain unclear. The application of single-cell Raman spectral analysis to plasmid–bacterial systems under different environmental conditions offers a new means of determining the impact of plasmids on host cell physiology, metabolic status, and response to stress