Phylogenomics,epigenomics, virulome and mobilome of Gram-negative bacteria co-resistant to carbapenems and polymyxins: a One Health systematic review and meta-analyses

Gram-negative bacteria (GNB) continue to develop resistance against important antibiotics including last-resort ones such as carbapenems and polymyxins. An analysis of GNB with co-resistance to carbapenems and polymyxins from a One Health perspective is presented. Data of species name, country, source of isolation, resistance genes (ARGs), plasmid type, clones and mobile genetic elements (MGEs) were deduced from 129 articles from January 2016 to March 2021. Available genomes and plasmids were obtained from PATRIC and NCBI. Resistomes and methylomes were analysed using BAcWGSTdb and REBASE whilst Kaptive was used to predict capsule typing. Plasmids and other MEGs were identified using MGE Finder and ResFinder. Phylogenetic analyses were done using RAxML and annotated with MEGA 7. A total of 877 isolates, 32 genomes and 44 plasmid sequences were analysed. Most of these isolates were reported in Asian countries and were isolated from clinical, animal and environmental sources. Colistin resistance was mostly mediated by mgrB inactivation (37%; n = 322) and mcr-1 (36%; n = 312), while OXA-48/181 was the most reported carbapenemase. IncX and IncI were the most common plasmids hosting carbapenemases and mcr genes. The isolates were co-resistant to other antibiotics, with floR (chloramphenicol) and fosA3 (fosfomycin) being common; E. coli ST156 and K. pneumoniae ST258 strains were common globally. Virulence genes and capsular KL-types were also detected. Type I, II, III and IV restriction modification systems were detected, comprising various MTases and restriction enzymes. The escalation of highly resistant isolates drains the economy due to untreatable bacterial infections, which leads to increasing global mortality rates and healthcare costs.     

Analysis of a Schnute postulate-based unified growth model for model selection in evolutionary computations

In order to evaluate the feasibility of a combined evolutionary algorithm-information theoretic approach to select the best model from a set of candidate invasive species models in ecology, and/or to evolve the most parsimonious model from a suite of competing models by comparing their relative performance, it is prudent to use a unified model that covers a myriad of situations. Using Schnute's postulates as a starting point [Schnute, J., 1981. A versatile growth model with statistically stable parameters, Can. J. Fish Aquat. Sci. 38, 1128-1140], we present a single, unified model for growth that can be successfully utilized for model selection in evolutionary computations. Depending on the parameter settings, the unified equation can describe several growth mechanisms. Such a generalized model mechanism, which encompasses a suite of competing models, can be successfully implemented in evolutionary computational algorithms to evolve the most parsimonious model that best fits ground truth data. We have done exactly this by testing the effectiveness of our reaction-diffusion-advection (RDA) model in an evolutionary computation model selection algorithm. The algorithm was validated (with success) against field data sets of the Zebra mussel invasion of Lake Champlain in the United States.     

Effect of self-association on the structural organization of partially folded proteins: inactivated actin

The propensity to associate or aggregate is one of the characteristic properties of many nonnative proteins. The aggregation of proteins is responsible for a number of human diseases and is a significant problem in biotechnology. Despite this, little is currently known about the effect of self-association on the structural properties and conformational stability of partially folded protein molecules. G-actin is shown to form equilibrium unfolding intermediate in the vicinity of 1.5 M guanidinium chloride (GdmCl). Refolding from the GdmCl unfolded state is terminated at the stage of formation of the same intermediate state. An analogous form, known as inactivated actin, can be obtained by heat treatment, or at moderate urea concentration, or by the release of Ca(2+). In all cases actin forms specific associates comprising partially folded protein molecules. The structural properties and conformational stability of inactivated actin were studied over a wide range of protein concentrations, and it was established that the process of self-association is rather specific. We have also shown that inactivated actin, being denatured, is characterized by a relatively rigid microenvironment of aromatic residues and exhibits a considerable limitation in the internal mobility of tryptophans. This means that specific self-association can play an important structure-forming role for the partially folded protein molecules.     

Nodulation of Thermopsis lupinoides by a Mesorhizobium huakuii strain with a unique nodA gene in Kamtchatka, Russia

Very little is known about rhizobia that form nodules on Thermopsis spp. We report the isolation of a Mesorhizobium huakuii strain with a unique nodA gene that form nodules on Thermopsis lupinoides in Kamtchatka, Russia. The isolate did not form nodules on Thermopsis chinensis or Thermopsis caroliniana, which suggests it may be host specific.     

Autophagy Gene Variant IRGM ?261T Contributes to Protection from Tuberculosis Caused by Mycobacterium tuberculosis but Not by M. africanum Strains

The human immunity-related GTPase M (IRGM) has been shown to be critically involved in regulating autophagy as a means of disposing cytosolic cellular structures and of reducing the growth of intracellular pathogens in vitro. This includes Mycobacterium tuberculosis, which is in agreement with findings indicating that M. tuberculosis translocates from the phagolysosome into the cytosol of infected cells, where it becomes exposed to autophagy. To test whether IRGM plays a role in human infection, we studied IRGM gene variants in 2010 patients with pulmonary tuberculosis (TB) and 2346 unaffected controls. Mycobacterial clades were classified by spoligotyping, IS6110 fingerprinting and genotyping of the pks1/15 deletion. The IRGM genotype −261TT was negatively associated with TB caused by M. tuberculosis (OR 0.66, CI 0.52–0.84, P_nominal 0.0009, P_corrected 0.0045) and not with TB caused by M. africanum or M. bovis (OR 0.95, CI 0.70–1.30. P 0.8). Further stratification for mycobacterial clades revealed that the protective effect applied only to M. tuberculosis strains with a damaged pks1/15 gene which is characteristic for the Euro-American (EUAM) subgroup of M. tuberculosis (OR 0.63, CI 0.49–0.81, P_nominal 0.0004, P_corrected 0.0019). Our results, including those of luciferase reporter gene assays with the IRGM variants −261C and −261T, suggest a role for IRGM and autophagy in protection of humans against natural infection with M. tuberculosis EUAM clades. Moreover, they support in vitro findings indicating that TB lineages capable of producing a distinct mycobacterial phenolic glycolipid that occurs exclusively in strains with an intact pks1/15 gene inhibit innate immune responses in which IRGM contributes to the control of autophagy. Finally, they raise the possibility that the increased frequency of the IRGM −261TT genotype may have contributed to the establishment of M. africanum as a pathogen in the West African population.     

Elevated Blood Lead Levels Are Associated with Reduced Risk of Malaria in Beninese Infants

Introduction

Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far.

Materials and Methods

Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed.

Results

At 12 months, the mean BLL of infants was 7.41 μg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 μg/dL. Lead poisoning, defined as BLL>10 μg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators.

Conclusion

Our study shows for the first time that BLL are negatively associated with malarial risk considering other risk factors. Malaria is one of the main causes of morbidity and mortality in infants under 5 years worldwide, and lead poisoning is the 6th most important contributor to the global burden of diseases measured in disability adjusted life years (DALYs) according to the Institute of Health Metrics. In conclusion, due to the high prevalence of elevated BLL, health interventions should look forward to minimize the exposure to lead to better protect the population in West Africa.     

Phone-based Intervention under Nurse Guidance after Stroke (PINGS): study protocol for a randomized controlled trial

BackgroundHypertension is the premier modifiable risk factor for recurrent stroke. In sub-Saharan Africa (SSA) where the stroke burden is escalating, little is known about the role of behavioral interventions in enhancing blood pressure (BP) control after stroke.Our objective is to test whether an m-Health technology-enabled, nurse-led, multilevel integrated approach is effective in improving BP control among Ghanaian stroke patients within 1 month of symptom onset compared with standard of care.MethodsThis two-arm cluster randomized controlled feasibility pilot trial will involve 60 recent-stroke survivors. Using a computer-generated sequence, patients will be randomly allocated into four clusters of 15 patients each per physician: two clusters in the intervention arm and two in the control arm. Patients in the intervention arm will receive a simple pillbox, a Blue-toothed UA-767Plus BT BP device and smartphone for monitoring and reporting BP measurements and medication intake under nurse guidance for 3 months. Tailored motivational text messages will be delivered based upon levels of adherence to the medication intake. Both groups will be followed up for 6 months to compare BP control at months 3, 6 and 9 as primary outcome measure. Physicians assessing BP control will be blinded to arms into which patients are allocated. Secondary outcome measures will include medication adherence scores and Competence and Autonomous Self-regulation Scale scores. A qualitative study is planned after follow-up to explore the lived experiences of participants in the intervention arm.DiscussionA feasible and preliminarily effective intervention would lead to a larger more definitive efficacy/effectiveness randomized controlled trial powered to look at clinical events, with the potential to reduce stroke-related morbidity and mortality in a low- to middle-income country.

Trial registration

ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02568137","term_id":"NCT02568137"}}NCT02568137, registered on 13 July 2015.

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1557-0) contains supplementary material, which is available to authorized users.     

小麦植株内糖类的昼夜变化

1.田间条件下灌浆期的小麦,叶子、叶鞘、及节间里的含糖量有着昼夜的变化,其中主要是蔗糖含量的变化。在日间下午3—6时含糖量最高,而晚上含糖量降低。2.小麦叶子、叶鞘及节间含糖量的变化受到环境因素的影响。这里主要是光线及植物社会的影响。3.在阴天只有单行植株第1叶和第2叶里的蔗糖有显著的昼夜变化;叶子、叶鞘变化很小,还维持了原来的水平。中行植株的叶子、叶鞘及节间的含糖量一般是降低的。4.在晴天,不问单行植株、中行植株,叶子、叶鞘和节间的含糖量都有昼夜的变化。但含糖量变化的进程在单行植株和中行植株之间有着很明显的差异。单行植株的含糖水/平高于中行植株。它们之间差异的幅度,越是在下部的器官越是显著。单行植株叶子、叶鞘的蔗糖最高含量在下午6时到达,而中行植株叶子、叶鞘里的蔗糖最高含量早在下午3时就达到了。这种差异的形成由于中行植株被左右边行的植株所荫蔽,在光线条件上处于不利的状态。在阴天中行植株的光线条件更差,以至阻碍了光合作用的进行。5.小麦在灌浆期,叶、叶鞘、节间糖的分布是这样的:叶子里的糖浓度小于叶鞘,叶鞘里的糖浓度小于节间的。但当阳光充足的时候,叶子里的浓度有时高于叶鞘中的浓度。此外第2节间的糖浓度高于第1节...