Two recently published randomized trials of doxycycline post exposure prophylaxis (PEP) have concluded that this intervention is highly effective at reducing the incidence of bacterial sexually transmitted infections (STIs) and has little or no risk of promoting the spread of antimicrobial resistance (AMR). In this perspective piece, we review four types of evidence that suggest that the risk of promoting AMR has been inadequately assessed in these studies. 1) The studies have all used proportion resistant as the outcome measure. This is a less sensitive measure of resistogenicity than MIC distribution. 2) These RCTs have not considered population-level pathways of AMR selection. 3) In populations with very high antimicrobial consumption such as PrEP cohorts, the relationship between antimicrobial consumption and resistance may be saturated. 4) Genetic linkage of AMR means that increased tetracycline use may select for AMR to not only tetracyclines but also other antimicrobials in STIs and other bacterial species. We recommend novel study designs to more adequately assess the AMR-inducing risk of doxycycline PEP.
The incidence of invasive fungal infections caused by Candida species is increasing, particularly in immunocompromised individuals. This increasing incidence poses a dual challenge, comprising escalating antifungal resistance and the necessity for accurate fungal identification. The Candida haemulonii complex further complicates these challenges due to limited identification tools. Like some other Candida species, infections involving this complex show resistance to multiple antifungals, requiring innovative therapeutic approaches. Rapamycin, known for its antifungal properties and immunosuppressive characteristics, was investigated against the C. haemulonii complex species. Results revealed a rapamycin minimal inhibitory concentration (MIC) range of 0.07 to >20 µM, with fungicidal effects in most strains. In vitro analyses using the rapamycin maximum plasma concentration (0.016 µM) showed reduced surface properties and decreased production of extracellular enzymes. Rapamycin also hindered biofilm formation by some strains. Even when treated at the human therapeutic dose, which is lower than the MIC, phenotypic variations in C. haemulonii were detected, hinting at the possible attenuation of some virulence factors when exposed to rapamycin.
The adoption of sustainable agricultural practices is increasingly imperative in addressing global food security and environmental concerns, with microbial based bio-inoculums emerging as a promising approach for nurturing soil health and fostering sustainable crop production.This review article explores the potential of microbial based bio-inoculumsor biofertilizers as a transformative approach toenhance plant disease resistance and growth. It explores the commercial prospects of biofertilizers, highlighting their role in addressing environmental concerns associated with conventional fertilizers while meeting the growing demand for eco-friendly agricultural practices. Additionally, this review discusses the future prospects of biofertilizers, emphasizing the ongoing advancements in biotechnology and formulation techniques that are expected to enhance their efficacy and applicability. Furthermore, this article provides insights into strategies for the successful acceptance of biofertilizers among farmers, including the importance of quality control, assurance, and education initiatives to raise awareness about their benefits and overcome barriers to adoption. By synthesizing the current research findings and industrial developments, this review offers valuable guidance for stakeholders seeking to exploit the potential of biofertilizers or beneficial microbes to promote soil health, ensure sustainable crop production, and addressing the challenges of modern agriculture.
Wastewater contains various emerging contaminants, including heavy metals, residues of pesticides, and pharmaceuticals. Therefore, irrigation with wastewater can enhance heavy metal contamination in soil and adversely affect plant growth. To mitigate this problem, plant growth-promoting bacteria (PGPR) can improve plant growth under heavy metal stress. This study aimed to isolate and characterize rhizospheric and endophytic bacteria from the rhizosphere soil and roots of a cucumber plant irrigated with municipal wastewater. A total of 121 morphologically distinct bacterial isolates from the rhizosphere and 90 bacterial isolates from the endophytic region were isolated and tested for heavy metal resistance and in vitro plant growth-promoting characteristics, including indole-3-acetic acid (IAA) production, phosphate solubilization, Hydrogen Cyanide (HCN) production, and siderophore production. Most of the bacteria analyzed from the rhizospheric and endophytic regions showed various plant growth-promoting characteristics and were tolerant to different heavy metals at various concentrations. Bacterial strains R1 (Proteus sp.) and E2 (Bacillus sp.) were antagonistic to Fusarium oxysporum f. sp. Lycopersici. Wastewater irrigation increases heavy metal-resistant bacteria in cucumber plants, which can alleviate heavy metal stress. Additionally, Proteus sp. and Bacillus sp. isolates are potential candidates for removing heavy metal-contaminated soil and could be potential biofertilizer candidates for selected plants and biocontrol agents.
The highly conserved hydrophobic pocket region of HIV-1 gp41 NHR triple-stranded coiled coil is crucial for the binding of CHR to NHR to form a six-helix bundle (6-HB). This pocket is only exposed instantaneously during fusion, making it an ideal target for antibody drug design. However, IgG molecule is too big to enter the pocket during the fusion process. Therefore, to overcome the steric hindrance and kinetic obstacles caused by the formation of gp41 pre-hairpin fusion intermediate, we obtained nanobodies (Nbs) targeting NHR by immunizing alpaca with an NHR-trimer mimic. Specifically, we identified a Nb, Nb-172, that exhibited potent and broadly neutralizing activity against HIV-1 pseudoviruses, HIV-1 primary isolates, and T20-resistant HIV-1 strains. In addition, the combinatorial use of mD1.22 and Nb-172 exhibited synergism in inhibiting HIV-1 infection inactivating cell-free virions. Nb-172 can competitively bind to the hydrophobic pocket of gp41 NHR to inhibit 6-HB formation. These findings suggest that Nb-172 merits further investigation as a potential therapeutic for HIV-1 infection.