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Biology subjects

Alam, M. Z.

Publications and source records attributed to Alam, M. Z..

8 recordsLinked to original sources

Gut microbiome-associated adaptability of suckermouth catfish inhabiting the polluted Buriganga River: insights into heavy-metal-remediating microorganisms

The suckermouth catfish (SMCF), known for its pollutant tolerance and high invasiveness, is prevalent in the heavily contaminated Buriganga River in Bangladesh. This waterway, contaminated with a variety of pollutants, including heavy metals, has experienced the near-complete disappearance of native fish populations; however, the suckermouth catfish demonstrates remarkable adaptability in this environment. One objective of this study is to elucidate the role of the gut microbiome in SMCFs' adaptation to this severely polluted habitat. We performed next-generation sequencing (NGS) of gut contents from SMCFs to analyze the gut microbial profiles of the fish samples. The results indicated that the suckermouth catfish's gut is enriched with microbial communities, including Paraclostridium, Klebsiella, Staphylococcus, Bacillus, and Pseudomonas, which have the potential to remediate pollutants, including heavy metals. The subsequent aim of this research is to isolate and identify bacteria from the SMCF gut capable of remediating multiple heavy metals. We isolated three isolates with the potential to remediate multiple heavy metals and identified them as Staphylococcus pasteuri SD, Morganella morganii SAS1, and Sporosarcina saromensis SAS using partial 16S rRNA gene amplicon sequencing and conventional techniques. All isolates showed distinct capabilities for remediating multiple heavy metals. Notably, S. pasteuri showed the highest lead (Pb) bioaccumulation (36.28%), S. saromensis showed the highest chromium (Cr) uptake (39.22%), and M. morganii showed the highest nickel (Ni) uptake (35.90%). Furthermore, these isolates exhibited remarkable metal-tolerance profiles, with maximum tolerable concentrations ranging from 125 ppm to 1000 ppm, and sustained healthy growth under metal-supplemented conditions throughout a 48-hour incubation period. This validates their potential to remediate multiple heavy metals. Collectively, the results underscore the ecological adaptability of suckermouth catfish in polluted aquatic environments, which is associated with their gut microbiome, and highlight the bioremediation potential of these gut-derived microbes as effective agents for mitigating heavy metal contamination.

microbiology↗

Immunotherapy restores therapeutic efficacy of fecal microbiome transplants to treat Clostridioides difficile

Microbiome-based therapeutics to treat enteric bacterial infections requires stable engraftment of transplanted beneficial bacteria that target and eliminate the pathogen. The host factors that determine whether a microbiome transplant engrafts remain largely unresolved. Here we demonstrate that Interleukin-10 (IL-10) signaling deficiency leads to impaired fecal microbiota transplantation (FMT) engraftment and failure to resolve Clostridioides difficile infection in mice. In the absence of IL-10-mediated immunoregulation provided by Foxp3+ Treg cells, increased IFN-{gamma} signaling in the intestine leads to elevated production of reactive oxygen/nitrogen species (ROS/RNS) by neutrophils and epithelial cells that supports the growth of inflammation-tolerant microbes, inhibits FMT engraftment, and impairs resolution of C. difficile. FMT treatment success can be restored by antibody-mediated blockade of IFN-{gamma} signaling, neutrophil depletion or inhibition of ROS/RNS production. Lastly, we developed an Il10-mRNA-LNP immunotherapy to boost IL-10 signaling in FMT Non-Responsive mice and demonstrate that Il10-mRNA-LNP administration is sufficient to restore FMT engraftment and subsequent resolution of C. difficile. Combined, these data support a mechanism by which IL-10 released by Treg cells limits IFN-{gamma} mediated intestinal inflammation thereby promoting an intestinal microenvironment receptive to FMT engraftment and resolution of C. difficile. These data demonstrate that the host's immune status can be therapeutically modulated to improve microbiome-based approaches to treat infection.

immunology↗

Clostridioides difficile toxin A and toxin B inhibit toxin-specific adaptive immune responses through glucosyltransferase-dependent activity

Clostridioides difficile colonizes the gastrointestinal tract and secretes two virulence factors: toxin A (TcdA) and toxin B (TcdB). Protective immunity against C. difficile infection is limited as patients are susceptible to multiple rounds of recurrent infections. The factors determining whether immunity to TcdA and TcdB is generated remain incompletely defined. We determined that C. difficile-infected mice generate antibody and IL-17A-producing CD4+ T cell responses to TcdA, but not TcdB. To determine the mechanism of the failed anti-TcdB immunity, C. difficile mutant strains expressing glucosyltransferase inactive (GTX) TcdA, and/or glucosyltransferase inactive TcdB were used. Infection with TcdBGTX or dual mutant (TcdAGTX TcdBGTX) restored TcdB-specific antibody responses, while infection with TcdAGTX or TcdAGTX TcdBGTX led to an earlier induction of TcdA-specific antibodies. Finally, infection with the dual GTX mutant enhanced TcdA and TcdB-specific CD4+ T cell responses. These data demonstrate that the glucosyltransferase activity of TcdA and TcdB hinders the antigen-specific adaptive immune response to itself and may be a mechanism that underlies high recurrence rates following C. difficile infection in patients.

immunology↗

CD34 serves as an intrinsic innate immune guardrail protecting stem cells from replicating retroviruses

Stem cells are highly resistant to viral infection compared to their differentiated progeny, and this resistance is associated with stem cell-specific restriction factors and intrinsic interferon stimulated genes (ISGs). In HIV infection, proviral DNA has been detected in certain bone marrow hematopoietic stem cells, yet widespread stem cell infection in vivo is restricted. Intriguingly, exposing bone marrow stem cells to HIV in vitro led to viral replication selectively only in the CD34- population, but not in the CD34+ cells. The mechanism dictating this CD34-based HIV restriction remained a mystery, especially since HIV has a capacity to antagonize restriction factors and ISGs. CD34 is a common marker of hematopoietic stem and progenitor cells. Here, we report the intrinsic antiviral properties of CD34. Expression of CD34 in HIV-1 producer cells results in the loss of progeny virion infectivity. Conversely, removal of CD34 using CRISPR/Cas9 knockout or stem cell differentiation cytokines promotes HIV-1 replication in stem cells. These results suggest that in addition to restriction factors and intrinsic ISGs, CD34 serves as a host innate protection preventing retrovirus replication in stem cells. Mechanistically, CD34 does not block viral entry, integration, and release. Instead, it becomes incorporated onto progeny virions, which inactivates virus infectivity. These findings offer new insights into innate immunity in stem cells, and highlight intriguing retrovirus-host interactions in evolution.

immunology↗

Global genome diversity of the Leishmania donovani complex

Protozoan parasites of the Leishmania donovani complex - L. donovani and L. infantum - cause the fatal disease visceral leishmaniasis. We present the first comprehensive genome-wide global study, with 151 cultured field isolates representing most of the geographical distribution. L. donovani isolates separated into five groups that largely coincide with geographical origin but vary greatly in diversity. In contrast, the majority of L. infantum samples fell into one globally-distributed group with little diversity. This picture is complicated by several hybrid lineages. Identified genetic groups vary in heterozygosity and levels of linkage, suggesting different recombination histories. We characterise chromosome-specific patterns of aneuploidy and identified extensive structural variation, including known and suspected drug resistance loci. This study reveals greater genetic diversity than suggested by geographically-focused studies, provides a resource of genomic variation for future work and sets the scene for a new understanding of the evolution and genetics of the Leishmania donovani complex.

genomics↗

Arbuscular mycorrhizal fungi, selenium, sulfur, silica-gel and biochar reduce arsenic uptake in plant biomass and improve nutritional quality in Pisum sativum

Arsenic (As) is a carcinogenic substance. It increased in crop grown in field soil from ground water irrigation. Subsequently As transport into the human body through food chains. The reduction of As transport in root, shoot and grain of pea genotypes is significantly important to protect human health. This research is focused on the biomass growth and alleviation of As accumulation in root, shoot and grain of pea genotypes in high As soil (30mgkg-1) amended with arbuscular mycorrhizal fungi (AMF), biochar (BC) of rice husk and saw dust, selenium (Se), silica- gel (Si), and sulfur (S). Shoot length, root, shoot and pod mass were generally higher in pea crops grown in soil amended with AMF, Se, Si- gel and S. Rice husk and saw dust BC less consistently increased some growth parameters, particularly in genotype BARI Motor 2. However, the BCs more often reduced growth and pod mass. All treatments significantly reduced As concentration in tissues; As in grains was reduced on average 60% by any of the soil amendments. AMF, Se and Si- gel all were found more effective than BC for the reduction of As uptake in pea crops. As in grains was reduced 77% by AMF, 71% by Se and 69% by Si- gel on average. As in root, shoot, and grain was also affected by variety; in control treatments, total As uptake in plants pot-1 of BARI Motor 1 and 3 was found 60 to 70% higher than BARI Motor 2. Comparing the variety and treatment with most As in grains (BARI Motor 1 control, 0.35 mg As kg-1) and least As in grains (BARI motor 1, 2 & 3 with AMF with 0.07 mg As kg-1), the choice of variety and soil amendment could reduce human intake of As through pea by 80%. It is recommended that choice of pea variety and soil amendment with AMF and Se have great potential for improving the nutritional quality of pea grown in As contaminated soil, as well as reducing As transfer to human bodies through food chains in pea crops.

microbiology↗

Hemozoin produced by mammals confers heme tolerance

Free heme is cytotoxic as exemplified by hemolytic diseases and genetic deficiencies in heme recycling and detoxifying pathways. Thus, intracellular accumulation of heme has not been observed in mammalian cells to date. Here we show that mice deficient for the heme transporter HRG1 accumulate over ten-fold excess heme in reticuloendothelial macrophage lysosomes that are 10 to 100 times larger than normal. Macrophages tolerate these high concentrations of heme by polymerizing them into crystalline hemozoin, which heretofore has only been found in blood-feeding parasites. HRG1 deficiency results in impaired erythroid maturation and an inability to systemically respond to iron deficiency. Complete heme tolerance requires a fully-operational heme degradation pathway as haploinsufficiency of HMOX1 combined with HRG1 inactivation causes perinatal lethality demonstrating synthetic lethal interactions between heme transport and degradation. Our studies establish the formation of hemozoin by mammals as a previously unsuspected heme tolerance pathway.

pathology↗

Arbuscular Mycorrhizal Fungus (AMF) and reduction of arsenic uptake in lentil crops

Arsenic (As) is a carcinogenic and hazardous substance that poses a serious risk to human health. Physiological studies have shown that growth of lentil crop have been impaired due to arsenic toxicity, and is transportable into human food chains. Our research focused on the transportation of As in lentil crops and its mitigation using Arbuscular Mycorrhizal Fungus (AMF). Shoot length, fresh and dry weight of shoot and root were found comparatively higher in 5 and 15 mgkg-1 arsenic treated lentil seedlings than in a 100 mgkg-1 As concentrated soil. As accumulation in lentils pods of BARI Mashur 1 were found higher than others; but As uptake in root and shoot were increased significantly in all BARI released lentil genotypes. Biomass growth of lentil was found higher in AMF treated soils in compare to non-AMF. AMF effectively reduced the arsenic uptake in root and shoot at 8 and 45 mgkg-1 As concentrated soils compared. As free lentil seeds are significantly important for human consumption through mitigation of As accumulation in lentil roots shoots and pods. AMF shows great potential in providing As free lentil seeds throughout the world.

microbiology↗