Bifunctional ArsI Dioxygenase from sp. ST3 with Both Methylarsenite [MAs(III)] Demethylation and MAs(III) Oxidation Activities.

Methylated arsenicals, including highly toxic species, such as methylarsenite [MAs(III)], are pervasive in the environment. Certain microorganisms possess the ability to detoxify MAs(III) by ArsI-catalyzed demethylation. Here, we characterize a bifunctional enzyme encoded by the gene from sp.

A Sb(III)-specific efflux transporter from Ensifer adhaerens E-60.

Antimony is pervasive environmental toxic substance, and numerous genes encoding mechanisms to resist, transform and extrude the toxic metalloid antimony have been discovered in various microorganisms. Here we identified a major facilitator superfamily (MFS) transporter, AntB, on the chromosome of the arsenite-oxidizing bacterium Ensifer adhaerens E-60 that confers resistance to Sb(III) and Sb(V). The antB gene is adjacent to gene encoding a LysR family transcriptional regulator termed LysR, which is an As(III)/Sb(III)-responsive transcriptional repressor that is predicted to control expression of antB.

Arsenate reductase of Rufibacter tibetensis is a metallophosphoesterase evolved to catalyze redox reactions.

An arsenate reductase (Car1) from the Bacteroidetes species Rufibacter tibetensis 1351 was isolated from the Tibetan Plateau. The strain exhibits resistance to arsenite [As(III)] and arsenate [As(V)] and reduces As(V) to As(III). Here we shed light on the mechanism of enzymatic reduction by Car1.

Anticancer Effects of the Trivalent Organoarsenical 2-Amino-4-(dihydroxyarsinoyl) Butanoate.

According to the National Cancer Institute, breast cancer is a leading cause of death in women. The lack of progesterone and estrogen receptors in triple-negative breast cancer (TNBC) cells results in a lack of response to hormonal, monoclonal, or tyrosine kinase inhibitor therapies. Despite intensive drug discovery, there is still no approved targeted treatment for TNBC.

Impact of Pre-Diagnostic Risk Factors on Short- and Long-Term Ovarian Cancer Survival Trajectories: A Longitudinal Observational Study.

Tumor- and treatment-related factors are established predictors of ovarian cancer survival. New studies suggest a differential impact of exposures on ovarian cancer survival trajectories (i.e.

Cervical cancer management in a low resource setting: A 10-year review in a tertiary care hospital in Kenya.

Background: Cervical cancer is one of the leading causes of cancer mortality among women in Kenya due to late presentations, poor access to health care, and limited resources. Across many low- and middle-income countries infrastructure and human resources for cervical cancer management are currently insufficient to meet the high population needs therefore patients are not able to get appropriate treatment.

Objective: This study aimed to describe the clinicopathological characteristics and the treatment profiles of cervical cancer cases seen at Moi Teaching and Referral Hospital (MTRH).

Fundamentals and application in phytoremediation of an efficient arsenate reducing bacterium Pseudomonas putida ARS1.

Arsenic is a ubiquitous environmental pollutant. Microbe-mediated arsenic bio-transformations significantly influence arsenic mobility and toxicity. Arsenic transformations by soil and aquatic organisms have been well documented, while little is known regarding effects due to endophytic bacteria.

Adaptation to metal(loid)s in strain Mucilaginibacter rubeus P2 involves novel arsenic resistance genes and mechanisms.

Arsenic is a ubiquitous environmental toxi substance that affects human health. Compared to inorganic arsenicals, reduced organoarsenicals are more toxic, and some of them are recognized as antibiotics, such as methylarsenite [MAs(III)] and arsinothricin (2-amino-4-(hydroxymethylarsinoyl)butanoate, or AST). To date, organoarsenicals such as MAs(V) and roxarsone [Rox(V)] are still used in agriculture and animal husbandry.

Widespread Distribution of the Gene Confers Bacterial Resistance to Environmental Antimony.

Microbial oxidation of environmental antimonite (Sb(III)) to antimonate (Sb(V)) is an antimony (Sb) detoxification mechanism. ST2, a bacterial isolate from a Sb-contaminated paddy soil, oxidizes Sb(III) to Sb(V) under oxic conditions by an unknown mechanism. Genomic analysis of ST2 reveals a gene of unknown function in an arsenic resistance (ars) operon that we term .

Arsenite Methyltransferase Diversity and Optimization of Methylation Efficiency.

Arsenic is methylated by arsenite (As(III)) -adenosylmethionine (SAM) methyltransferases (ArsMs). ArsM crystal structures show three domains (an N-terminal SAM binding domain (A domain), a central arsenic binding domain (B domain), and a C-terminal domain of unknown function (C domain)). In this study, we performed a comparative analysis of ArsMs and found a broad diversity in structural domains.

Arsinothricin Inhibits Proliferation in Blood and Blocks Parasite Transmission to Mosquitoes.

Malaria, caused by protozoal parasites, remains a leading cause of morbidity and mortality. The parasite has a complex life cycle, with asexual and sexual forms in humans and mosquitoes. Most antimalarials target only the symptomatic asexual blood stage.

Anoxygenic phototrophic arsenite oxidation by a Rhodobacter strain.

Microbially mediated arsenic redox transformations are key for arsenic speciation and mobility in rice paddies. Whereas anaerobic anoxygenic photosynthesis coupled to arsenite (As(III)) oxidation has been widely examined in arsenic-replete ecosystems, it remains unknown whether this light-dependent process exists in paddy soils. Here, we isolated a phototrophic purple bacteria, Rhodobacter strain CZR27, from an arsenic-contaminated paddy soil and demonstrated its capacity to oxidize As(III) to arsenate (As(V)) using malate as a carbon source photosynthetically.

The ArsQ permease and transport of the antibiotic arsinothricin.

The pentavalent organoarsenical arsinothricin (AST) is a natural product synthesized by the rhizosphere bacterium Burkholderia gladioli GSRB05. AST is a broad-spectrum antibiotic effective against human pathogens such as carbapenem-resistant Enterobacter cloacae. It is a non-proteogenic amino acid and glutamate mimetic that inhibits bacterial glutamine synthetase.

Selective Methylation by an ArsM -Adenosylmethionine Methyltransferase from GSRB05 Enhances Antibiotic Production.

Arsenic methylation contributes to the formation and diversity of environmental organoarsenicals, an important process in the arsenic biogeochemical cycle. The gene encoding an arsenite (As(III)) -adenosylmethionine (SAM) methyltransferase is widely distributed in members of every kingdom. A number of ArsM enzymes have been shown to have different patterns of methylation.

A PadR family transcriptional repressor controls transcription of a trivalent metalloid resistance operon of Azospirillum halopraeferens strain Au 4.

Methylarsenite [MAs(III)] is a highly toxic arsenical produced by some microbes as an antibiotic. In this study, we demonstrate that a PadR family transcriptional regulator, PadR , from Azospirillum halopraeferens strain Au 4 directly binds to the promoter region of the arsenic resistance (ars) operon (consisting of padR , arsV, and arsW) and represses transcription of arsV and arsW genes involved in MAs(III) resistance. Quantitative reverse transcriptase PCR and transcriptional reporter assays showed that transcription of the ars operon is induced strongly by MAs(III) and less strongly by arsenite and antimonite.

Chemical synthesis of the organoarsenical antibiotic arsinothricin.

We report two routes of chemical synthesis of arsinothricin (AST), the novel organoarsenical antibiotic. One is by condensation of the 2-chloroethyl(methyl)arsinic acid with acetamidomalonate, and the second involves reduction of the -acetyl protected derivative of hydroxyarsinothricin (AST-OH) and subsequent methylation of a trivalent arsenic intermediate with methyl iodide. The enzyme AST -acetyltransferase (ArsN1) was utilized to purify l-AST from racemic AST.

The ArsI C-As lyase: Elucidating the catalytic mechanism of degradation of organoarsenicals.

Organoarsenicals such as monosodium methylarsenate (MSMA or MAs(V)) and roxarsone (4-hydroxyl-3-nitrophenylarsenate or Rox(V)) have been extensively used as herbicides and growth enhancers for poultry, respectively. Degradation of organoarsenicals to inorganic arsenite (As(III)) contaminates crops and drinking water. One such process is catalyzed by the bacterial enzyme ArsI, whose gene is found in many soil bacteria.

ArsZ from Ensifer adhaerens ST2 is a novel methylarsenite oxidase.

Trivalent methylarsenite [MAs(III)] produced by biomethylation is more toxic than inorganic arsenite [As(III)]. Hence, MAs(III) has been proposed to be a primordial antibiotic. Other bacteria evolved mechanisms to detoxify MAs(III).

Epidemiological profile and clinico-pathological features of pediatric gynecological cancers at Moi Teaching & Referral Hospital, Kenya.

Background: The main pediatric (0-18 years) gynecologic cancers include stromal carcinomas (juvenile granulosa cell tumors and Sertoli-Leydig cell tumors), genital rhabdomyosarcomas and ovarian germ cell. Outcomes depend on time of diagnosis, stage, tumor type and treatment which can have long-term effects on the reproductive career of these patients. This study seeks to analyze the trends in clinical-pathologic presentation, treatment and outcomes in the cases seen at our facility.

An ArsRC fusion protein enhances arsenate sensing and detoxification.

Arsenical resistance (ars) operons encode genes for arsenic resistance and biotransformation. The majority are composed of individual genes, but fusion of ars genes is not uncommon, although it is not clear if the fused gene products are functional. Here we report identification of a four-gene ars operon from Paracoccus sp.

Arsenic in medicine: past, present and future.

Arsenicals are one of the oldest treatments for a variety of human disorders. Although infamous for its toxicity, arsenic is paradoxically a therapeutic agent that has been used since ancient times for the treatment of multiple diseases. The use of most arsenic-based drugs was abandoned with the discovery of antibiotics in the 1940s, but a few remained in use such as those for the treatment of trypanosomiasis.

Insights into S-adenosyl-l-methionine (SAM)-dependent methyltransferase related diseases and genetic polymorphisms.

Enzymatic methylation catalyzed by methyltransferases has a significant impact on many human biochemical reactions. As the second most ubiquitous cofactor in humans, S-adenosyl-l-methionine (SAM or AdoMet) serves as a methyl donor for SAM-dependent methyltransferases (MTases), which transfer a methyl group to a nucleophilic acceptor such as O, As, N, S, or C as the byproduct. SAM-dependent methyltransferases can be grouped into different types based on the substrates.

ArsV and ArsW provide synergistic resistance to the antibiotic methylarsenite.

Toxic organoarsenicals enter the environment from biogenic and anthropogenic activities such as microbial methylation of inorganic arsenic and pentavalent herbicides such as monosodium methylarsenate (MSMA or MAs(V)). Trivalent MAs(III) is considerably more toxic than arsenite or arsenate. Microbes have evolved mechanisms to detoxify organoarsenicals.