Spread Of Antibiotic Resistance Research Articles

Domesticated conjugation machinery promotes DNA exchange in hyperthermophilic archaea.

Conjugation, a major mechanism of horizontal gene transfer promoting the spread of antibiotic resistance among human pathogens, involves establishing a junction between a donor and a recipient cell. The mating pilus plays a prominent role in this process. In bacteria, the conjugation machinery is encoded by plasmids or transposons and typically mediates the transfer of cognate mobile genetic elements. Much less has been known about conjugation in archaea, with no homologs of bacterial mating pilins having been identified in sequence searches. Here, using cryo-electron microscopy, we determined high-resolution structures of three conjugative pili, two from hyperthermophilic archaea, Aeropyrum pernix and Pyrobaculum calidifontis, and one encoded by the Ti plasmid of the bacterium Agrobacterium tumefaciens. We show that the archaeal pili are homologous to bacterial mating pili and display intricate pilin-lipid interaction networks. Unlike in bacteria, the conjugation machinery in hyperthermophilic archaea has been domesticated and mediates the transfer of cellular DNA. We suggest that the constitutive expression of the pili may be due to the chronic damage of DNA at high temperatures that is constantly being repaired using homologous recombination.

An expectation-maximization algorithm for estimating proportions of deletions among bacterial populations with application to study antibiotic resistance gene transfer in Enterococcus faecalis.

The online version contains supplementary material available at 10.1007/s42995-022-00144-z.

Nanotechnology as a Promising Approach to Combat Multidrug Resistant Bacteria: A Comprehensive Review and Future Perspectives.

The wide spread of antibiotic resistance has been alarming in recent years and poses a serious global hazard to public health as it leads to millions of deaths all over the world. The wide spread of resistance and sharing resistance genes between different types of bacteria led to emergence of multidrug resistant (MDR) microorganisms. This problem is exacerbated when microorganisms create biofilms, which can boost bacterial resistance by up to 1000-fold and increase the emergence of MDR infections. The absence of novel and potent antimicrobial compounds is linked to the rise of multidrug resistance. This has sparked international efforts to develop new and improved antimicrobial agents as well as innovative and efficient techniques for antibiotic administration and targeting. There is an evolution in nanotechnology in recent years in treatment and prevention of the biofilm formation and MDR infection. The development of nanomaterial-based therapeutics, which could overcome current pathways linked to acquired drug resistance, is a hopeful strategy for treating difficult-to-treat bacterial infections. Additionally, nanoparticles' distinct size and physical characteristics enable them to target biofilms and treat resistant pathogens. This review highlights the current advances in nanotechnology to combat MDR and biofilm infection. In addition, it provides insight on development and mechanisms of antibiotic resistance, spread of MDR and XDR infection, and development of nanoparticles and mechanisms of their antibacterial activity. Moreover, this review considers the difference between free antibiotics and nanoantibiotics, and the synergistic effect of nanoantibiotics to combat planktonic bacteria, intracellular bacteria and biofilm. Finally, we will discuss the strength and limitations of the application of nanotechnology against bacterial infection and future perspectives.

Identification of Novel Mobile Genetic Elements Associated with Resistance to Macrolide and Lincosamide in Streptococcus dysgalactiae subsp. equisimilis

Background: Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an important human pathogen. Recently, several studies have described the incidence of antibiotic resistance for SDSE worldwide, however, the data on the presence of corresponding genes and their possible association with mobile genetic elements are still limited. Objective: The objective of this research was to analyze the macrolide resistance in SDSE and to identify genetic determinants, mechanisms of resistance, and association with mobile genetic elements. Methods: A total of 9 SDSE strains from the collection of Joint Russian-Vietnamese Tropical Research and Technological Center (Hanoi, Vietnam) were used. These strains were previously isolated from throat swabs of children with pharyngotonsillitis in 6 provinces in Vietnam from 2012 to 2015. Antimicrobial resistance was tested by disk diffusion method. The presence of antibiotic resistance genes (ARG) was analyzed by PCR. The strains were characterized by emm typing and multilocus sequence typing (MLST). Illumina sequencing was employed for genome analysis of 4 representative SDSE isolates. Analysis of genetic elements with antibiotic resistance determinants was done using PubMed database and BLAST-searches. Artemis was used for comparative analysis of genetic elements. Results: In our study, we identified emm types that were similar to those reported in other studies. All SDSE isolates remained susceptible to penicillin, but presented alarming level of resistance to macrolides, tetracyclines, and fluoroquinolones. Most of the erythromycin-resistant strains were also characterized by clindamycin-resistance (MLSB phenotype). Both erm and different alleles of mef genes widely distributed among streptococcus pyogenes and Streptococcus pneumoniae were detected, except erm (TR) gene. The genetic elements carrying resistance determinants showed significant interspecies similarities, indicating conjugative transfer of antibiotic resistance genes between streptococcal species. Conclusion: Identification of the novel antibiotic resistance genes in SDSE indicates the necessity of monitoring of antibiotic resistance spreading and gene transfer in this bacterium.

Effects of Perinatal Antibiotic Exposure and Neonatal Gut Microbiota

Antibiotic therapy is one of the most important strategies to treat bacterial infections. The overuse of antibiotics, especially in the perinatal period, is associated with long-lasting negative consequences such as the spread of antibiotic resistance and alterations in the composition and function of the gut microbiota, both of which negatively affect human health. In this review, we summarize recent evidence about the influence of antibiotic treatment on the neonatal gut microbiota and the subsequent negative effects on the health of the infant. We also analyze the possible microbiome-based approaches for the re-establishment of healthy microbiota in neonates.

Profiling of Antibiotic Residues in Surface Water of River Yamuna Stretch Passing through Delhi, India

The River Yamuna is one of the largest rivers in northern India. It serves as a major source of potable water to the National Capital Delhi. A study was carried out to monitor and quantify three common antibiotics in surface water, with the help of Ultra-Performance Liquid Chromatography (UPLC) coupled with the Mass spectrophotometer (MS/MS)-based method. All the major river water locations in the research area were sampled in triplicate to determine the significant presence of antibiotics from local areas, hospitals, drug manufacturing facilities, and residential areas. Using spiked, as well as actual samples, an optimized method for the detection and quantification of different concentrations of antibiotics was developed. Spatiotemporal variations in the physicochemical properties at the five sites, including reference site-6 (Jamia Millia Islamia), during the pre-monsoon and post-monsoon period, were also investigated. Maximum concentration was observed during the pre-monsoon season followed by the post-monsoon season. The highest detected antibiotic concentration from the river water samples was that of ofloxacin (145.3794 ng/mL), followed by amoxicillin (3.033 ng/mL) and erythromycin (2.171 ng/mL). An aquatic environment may be very vulnerable to dangers from these pharmaceutical residues, according to this risk assessment. Additionally, the levels and compositions of pharmaceutical residue in the aquatic ecosystem might be influenced by seasonal agricultural application, precipitation, and temperature. The findings revealed the existence of antibiotics because of their indiscriminate usage, which may have resulted in the development of resistant strains and ultimately contributed to the spread of antibiotic resistance among living organisms in the river. Thus, attention is required particularly to this section of river as it is the local lifeline source for urban consumers for the domestic water supply and farmers for cultivation.

Results of dynamic monitoring of the spectrum of bacterial causes of acute urinary tract infections in children

The aim of the study: to explore in dynamics the structure of pathogens in children of Zaporizhzhia region with acute urinary tract infections and the possible changes in their antibiotic susceptibility. Materials and methods. We analysed results of urine culture in 439 children aged 4 to 18 years with acute urinary tract infection (293 patients in 2014–2016 and 146 patients in 2018–2020). Determination of bacterial species and susceptibility to antibiotics was performed on a bacteriological analyzer VITEK 2 COMPACT (bioMerieux, France) using AES software: Global CLSI-based + Phenotypic (2014, 2018) in accordance with CLSI and EUCAST tables. The coefficient of antibiotic resistance was additionally calculated for each isolate. Results. According to the analysis of bacteriological monitoring, it was found that in 2018–2020 compared to 2014–2016 among the causative agents of acute urinary tract infections in children, the role of gram-negative bacteria had raised due to increasing the proportion of Escherichia сoli and Proteus mirabilis. Gram-positive microflora has been represented by bacteria of the genus Enterococcus, in 2018–2020 in most samples was isolated Enterococcus faecium (28.1 %), in 2014–2016 among the representatives Enterococcus faecalis prevailed (38.9 %). The analysis of antibiotic resistance showed that in 2018–2020 the number of resistant strains of E. coli to amikacin increased 6.8 times to 2014–2016 (Р < 0.01) and there was a decrease in the sensitivity of Enterococcus to aminopenicillins from 91.4 % to 41.3 % (P < 0.01). Among bacteria of the genus Enterococcus the average values of the coefficient of resistance to antibiotics in 2018–2020 increased 3.75 times compared to 2014–2016 due to a 2.3-fold increase in the frequency of multidrug-resistant strains (P < 0.05). Conclusions. The obtained data are convincing evidence of the need for mandatory bacteriological examination of urine before antibacterial therapy to increase the effectiveness of therapeutic measures, prevention of the emergence and spread of antibiotic resistance. An increase in resistance of E. coli to amikacin and Enterococcus spp. to ampicillin does not allow the use of these drugs as empirical therapy of acute urinary tract infections in children.

High performance electroactive ultrafiltration membrane for antibiotic resistance removal from wastewater effluent

As emerging contaminants, antibiotic and antibiotic resistance genes (ARGs) in wastewater effluent induce and increase the risk of antibiotic resistance spreading in the environment. Herein, we fabricated a series of polyaniline/carbon nanotube-assisted electroactive membranes (PANI/CNT-EMs) to remove low-concentration antibiotics (i.e., sulfamethoxazole, SMX), antibiotic-resistant bacteria (ARB), and ARGs, thus reducing ecotoxicity and antibiotic resistance pollution in wastewater effluent. The PANI/CNT-EMs possess excellent electrochemical properties with a uniform and stable structure. Compared with pristine EMs, the PANI/CNT-EMs effectively enhanced SMX degradation and substantially lessened the ecotoxicity of the degradation products. The PANI/CNT-EMs show higher inactivation ability in intercepted ARB and significant degradation of both intracellular and extracellular ARGs (iARGs and eARGs) during wastewater effluent electrofiltration under a low voltage of +2 V. More importantly, the reduced integron (i.e., intI1) abundance and ARG transfer frequency further demonstrated that the PANI/CNT-EMs are more conducive to controlling the spread of antibiotic resistance. Furthermore, compared with pristine EMs, the antifouling property of PANI/CNT-EMs is improved by 42.1% during wastewater effluent treatment. Overall, these findings offer a promising approach for antibiotic resistance control in wastewater effluent treatment.

Precise Photothermal Treatment of Methicillin-Resistant S. aureus Infection via Phage Lysin-Cell Binding Domain-Modified Gold Nanosheets.

The increasing spread of antibiotic resistance in bacterial pathogens poses a huge threat to global human health. Precise targeting of bacterial pathogens while avoiding collateral damage to healthy tissues has become the overriding goal for bacterial infection treatment. Inspired by the host specificity of bacteriophages, a biomimetic intelligent platform was designed for highly precise photothermal treatment herein. As proof-of-concept, the lysin cell-binding domain (CBD) from a newly discovered virulent methicillin-resistant S. aureus (MRSA) phage Z was applied to the functionalization of gold nanosheets. Our results demonstrated that the bionanocomposite gold particles (Au@PEG-CBDz) could be effectively delivered directly to MRSA and kill them effectively under near infrared irradiation in vitro, while displaying good in vivo biocompatibility. This work is the first to report the combination of phage lysin navigatory function with photothermal effect-induced bactericidal activity from Au nanosheets, providing a novel therapeutic mode for the precision treatment of antibiotic-resistant bacterial infections.

The fate of sulfonamide resistance genes and anthropogenic pollution marker intI1 after discharge of wastewater into a pristine river stream.

Currently there are sparse regulations regarding the discharge of antibiotics from wastewater treatment plants (WWTP) into river systems, making surface waters a latent reservoir for antibiotics and antibiotic resistance genes (ARGs). To better understand factors that influence the fate of ARGs in the environment and to foster surveillance of antibiotic resistance spreading in such habitats, several indicator genes have been proposed, including the integrase gene intI1 and the sulfonamide resistance genes sul1 and sul2. Here we used quantitative PCR and long-read nanopore sequencing to monitor the abundance of these indicator genes and ARGs present as class 1 integron gene cassettes in a river system from pristine source to WWTP-impacted water. ARG abundance was compared with the dynamics of the microbial communities determined via 16S rRNA gene amplicon sequencing, conventional water parameters and the concentration of sulfamethoxazole (SMX), sulfamethazine (SMZ) and sulfadiazine (SDZ). Our results show that WWTP effluent was the principal source of all three sulfonamides with highest concentrations for SMX (median 8.6 ng/l), and of the indicator genes sul1, sul2 and intI1 with median relative abundance to 16S rRNA gene of 0.55, 0.77 and 0.65%, respectively. Downstream from the WWTP, water quality improved constantly, including lower sulfonamide concentrations, decreasing abundances of sul1 and sul2 and lower numbers and diversity of ARGs in the class 1 integron. The riverine microbial community partially recovered after receiving WWTP effluent, which was consolidated by a microbiome recovery model. Surprisingly, the relative abundance of intI1 increased 3-fold over 13 km of the river stretch, suggesting an internal gene multiplication. We found no evidence that low amounts of sulfonamides in the aquatic environment stimulate the maintenance or even spread of corresponding ARGs. Nevertheless, class 1 integrons carrying various ARGs were still present 13 km downstream from the WWTP. Therefore, limiting the release of ARG-harboring microorganisms may be more crucial for restricting the environmental spread of antimicrobial resistance than attenuating ng/L concentrations of antibiotics.

High-pressure processing effect on conjugal antibiotic resistance genes transfer in vitro and in the food matrix among strains from starter cultures

This study analyzed the effect of high-pressure processing (HPP) on the frequency of conjugal gene transfer of antibiotic resistance genes among strains obtained from starter cultures. Gene transfer ability was analyzed in vitro and in situ in the food matrix. It was found that the transfer of aminoglycoside resistance genes did not occur after high-pressure treatment, either in vitro or in situ. After exposure to HPP, the transfer frequencies of tetracycline, ampicillin and chloramphenicol resistance genes increased significantly compared to the control sample, both in vitro and in situ. The frequency of resistance genes transfer in the food matrix in the pressurized samples did not differ significantly from the in vitro transfer rate. Minimum Inhibitory Concentrations (MICs) for these antibiotics determined for transconjugants were lower or equal to MICs determined for the donors. No significant differences were observed between the MIC values determined for the transconjugants obtained in vitro and in situ. The results suggest that HPP may contribute to the spread of antibiotic resistance. This points to the need to verify starter cultures strains for their antibiotic resistance and pressurization parameters to avoid spreading antibiotic resistance genes.

Quorum‐sensing interference in vibrios

AbstractVibrios belonging to the Harveyi clade and the Splendidus clade are important pathogens that cause high economic losses in aquaculture. To control bacterial diseases, antibiotics have been widely applied in aquaculture worldwide for many years, contributing to the development and spread of antibiotic resistance. To further limit the use of antibiotics without affecting the envisaged sustainable growth of the sector, novel therapies to control diseases are urgently needed. As the virulence of many bacterial pathogens is controlled by quorum sensing, quorum‐sensing interference has been the most intensively studied antivirulence therapy. It aims to disarm rather than kill the pathogens to prevent them from attacking their host. This strategy is believed to impose less selective pressure upon pathogens for resistance development when compared to antibiotics. In this review, we provide an overview of quorum‐sensing systems in vibrios belonging to the Harveyi clade and the Splendidus clade, as well as the virulence‐related phenotypes controlled by these systems. The major quorum‐sensing systems in these bacteria include three‐channel quorum‐sensing systems and indole signalling. Furthermore, we discuss different agents that interfere with quorum‐sensing systems and that protect aquatic animals from disease caused by Harveyi clade and Splendidus clade vibrios. These agents include small molecules (both natural and synthetic) that interfere with three‐channel quorum‐sensing systems or with indole signalling and signal molecule‐degrading bacteria. Finally, we identify knowledge gaps and propose some frontiers for further research in order to move this promising field forward.

Structural and functional characterization of TraI from pKM101 reveals basis for DNA processing.

Type 4 secretion systems are large and versatile protein machineries that facilitate the spread of antibiotic resistance and other virulence factors via horizontal gene transfer. Conjugative type 4 secretion systems depend on relaxases to process the DNA in preparation for transport. TraI from the well-studied conjugative plasmid pKM101 is one such relaxase. Here, we report the crystal structure of the trans-esterase domain of TraI in complex with its substrate oriT DNA, highlighting the conserved DNA-binding mechanism of conjugative relaxases. In addition, we present an apo structure of the trans-esterase domain of TraI that includes most of the flexible thumb region. This allows us for the first time to visualize the large conformational change of the thumb subdomain upon DNA binding. We also characterize the DNA binding, nicking, and religation activity of the trans-esterase domain, helicase domain, and full-length TraI. Unlike previous indications in the literature, our results reveal that the TraI trans-esterase domain from pKM101 behaves in a conserved manner with its homologs from the R388 and F plasmids.

Hazard reduction and persistence of risk of antibiotic resistance during thermophilic composting of animal waste

Animal production contributes substantially to the dissemination of antibiotic resistance genes (ARGs) in the environment. Thermophilic composting is cost-effective for reducing hazards in animal wastes. However, ARGs can still persist in composts and the mechanism remains largely unclear. In the present study, metagenomics and real-time quantitative PCR were employed to assess the dynamics of ARGs, especially those of high risk to human health, their host species and pathogenicity of the bacterial community during thermophilic composting of chicken manure. The results showed that thermophilic composting was effective at reducing the majority of the spreading risk of antibiotic resistance by 1) eliminating more than half of allARGs that accounted for 80% of the total abundance, 2) reducing the number and abundance of high-risk ARGs significantly, and 3) removing the ARG hosts and the pathogenicity of the bacterial community substantially. The attenuation of ARGs was primarily driven by the bacterial community succession. However, the abundance of some ARGs, especially those associated with plasmids, rebounded during the cooling phase, likely caused by horizontal gene transfer. Our research reveals that minimising the horizontal transfer of plasmid-associated ARGs during the cooling phase of thermophilic composting is crucial for a more effective reduction of the hazards associated with the spread of antibiotic resistance.

The ESKAPE mobilome contributes to the spread of antimicrobial resistance and CRISPR-mediated conflict between mobile genetic elements

Mobile genetic elements (MGEs) mediate the shuffling of genes among organisms. They contribute to the spread of virulence and antibiotic resistance (AMR) genes in human pathogens, such as the particularly problematic group of ESKAPE pathogens. Here, we performed the first systematic analysis of MGEs, including plasmids, prophages, and integrative and conjugative/mobilizable elements (ICEs/IMEs), across all ESKAPE pathogens. We found that different MGE types are asymmetrically distributed across these pathogens, and that most horizontal gene transfer (HGT) events are restricted by phylum or genus. We show that the MGEs proteome is involved in diverse functional processes and distinguish widespread proteins within the ESKAPE context. Moreover, anti-CRISPRs and AMR genes are overrepresented in the ESKAPE mobilome. Our results also underscore species-specific trends shaping the number of MGEs, AMR, and virulence genes across pairs of conspecific ESKAPE genomes with and without CRISPR-Cas systems. Finally, we observed that CRISPR spacers found on prophages, ICEs/IMEs, and plasmids have different targeting biases: while plasmid and prophage CRISPRs almost exclusively target other plasmids and prophages, respectively, ICEs/IMEs CRISPRs preferentially target prophages. Overall, our study highlights the general importance of the ESKAPE mobilome in contributing to the spread of AMR and mediating conflict among MGEs.

Environmental drivers and interaction mechanisms of heavy metal and antibiotic resistome exposed to amoxicillin during aerobic composting.

The environmental accumulation and spread of antibiotic resistance pose a major threat to global health. Aerobic composting has become an important hotspot of combined pollution [e.g., antibiotic resistance genes (ARGs) and heavy metals (HMs)] in the process of centralized treatment and resource utilization of manure. However, the interaction mechanisms and environmental drivers of HMs resistome (MRGs), antibiotic resistance (genotype and phenotype), and microbiome during aerobic composting under the widely used amoxicillin (AMX) selection pressure are still poorly understood. Here, we investigated the dynamics of HMs bioavailability and their MRGs, AMX-resistant bacteria (ARB) and antibiotic resistome (ARGs and intI1), and bacterial community to decipher the impact mechanism of AMX by conducting aerobic composting experiments. We detected higher exchangeable HMs and MRGs in the AMX group than the control group, especially for the czrC gene, indicating that AMX exposure may inhibit HMs passivation and promote some MRGs. The presence of AMX significantly altered bacterial community composition and AMX-resistant and -sensitive bacterial structures, elevating antibiotic resistome and its potential transmission risks, in which the proportions of ARB and intI1 were greatly increased to 148- and 11.6-fold compared to the control group. Proteobacteria and Actinobacteria were significant biomarkers of AMX exposure and may be critical in promoting bacterial resistance development. S0134_terrestrial_group was significantly negatively correlated with blaTEM and czrC genes, which might play a role in the elimination of some ARGs and MRGs. Except for the basic physicochemical (MC, C/N, and pH) and nutritional indicators (NO3 --N, NH4 +-N), Bio-Cu may be an important environmental driver regulating bacterial resistance during composting. These findings suggested the importance of the interaction mechanism of combined pollution and its synergistic treatment during aerobic composting need to be emphasized.

Effect of CeO2 Nanoparticles on the Spread of Antibiotic Resistance in a Reclaimed Water-Soil-Radish System - Shenzhen City, Guangdong Province, China, April 2023.

The use of reclaimed water (RW) for irrigation in agricultural practices raises concerns regarding the dissemination of antibiotic resistance genes (ARGs) from soils to edible crops. The effectiveness of nanoparticles (NPs) in reducing antibiotic resistance in vegetables irrigated with RW remains largely unexplored. To investigate the effects, we conducted pot experiments in which radishes were planted in soil amended with CeO2 NPs using various application techniques. The abundance of ARGs was characterized using high-throughput quantitative PCR (HT-qPCR). Concurrently, we utilized 16S ribosomal RNA (rRNA) gene sequencing to evaluate the microbial community structure of both the rhizosphere soil and the endophytic compartment within the radishes. Employing bioinformatics analysis, we probed the potential mechanisms by which NPs influence the resistome within the reclaimed water-soil-radish system. Following the application of CeO2 NPs, there was a noticeable reduction in both the number and concentration of ARG genotypes in the rhizosphere soil, as well as within the radish. Concurrently, CeO2 NPs appeared to mitigate the propagation of ARGs within the reclaimed water-soil-radish system. The ability of CeO2 NPs to modulate the resistome is linked to alterations in microbial community structure. Soil treatment with NPs emerged as the most effective strategy for curbing the spread of ARGs. This finding provides a theoretical foundation for the development of nano-agricultural technologies aimed at controlling the proliferation of ARGs.

Antibiotic concentrations and antibiotic resistance in aquatic environments of the WHO Western Pacific and South-East Asia regions: a systematic review and probabilistic environmental hazard assessment

Antibiotic resistance poses human health risks, and there are concerns about the effect of environmental antibiotic residues in the selection and spread of antibiotic resistance. The aim of this study was to identify antibiotic residue levels that are likely to select for resistance and relative contributions from different aquatic sources, of various aquatic environmental compartments of the WHO Western Pacific region (WPR) and the WHO South-East Asia region (SEAR), including in China and India. A systematic review of empirical studies that measured antibiotic concentrations in aquatic environments, published between 2006 and 2019, and a probabilistic environmental hazard assessments approach, were used to identify antibiotic concentrations that are likely to select for resistance in various aquatic environmental compartments of the WPR and SEAR, including in China and India. The assessment involved the use of measured environmental concentrations and predicted no-effect concentrations (PNECs). The systematic review found 218 relevant studies of 5230 screened from the WPR and 22 relevant studies of 2625 screened from the SEAR; some of these relevant studies were largely from China (n=168) and India (n=15). 92 antibiotics in the WPR and 45 in the SEAR were detected in various aquatic compartments. Antibiotic concentrations that most likely exceeded PNECs (0-100%) were observed in wastewater, and influents and effluents of wastewater treatment plants. Antibiotic concentrations that most likely exceeded PNECs were also observed in aquatic environmental compartments. The highest risk for the development of resistance was in tap or drinking water of the WPR and China for ciprofloxacin (62·5%). The relative contributions of potential sources of antibiotic contamination in waterways, such as hospitals, municipals, livestock, and pharmaceutical manufacturing, was determined for each antibiotic. The concentrations of antibiotic residues found in wastewater and wastewater treatment plants of the WPR and SEAR make them potential hotspots for the development of antibiotic resistance, which creates human health risks from environmental exposure via drinking water. These findings can help decision makers to target risk reduction measures against environmental residues of priority antibiotics in high-risk sites, and help to focus research efforts in these world regions. Swedish Research Council.

H2S-removing UiO-66 MOFs for sensitized antibacterial therapy.

Antibiotic tolerance is implicated in difficult-to-treat infections and the development and spread of antibiotic resistance. The high storage capacities and excellent biocompatibilities of UiO-66-based metal-organic frameworks (MOFs) have made them emerging candidates as drug-delivery vectors. In view of hydrogen sulfide (H2S) having been associated with the development of intrinsic resistance to antibacterial agents, we designed a strategy to potentiate existing antibiotics by eliminating bacterial endogenous H2S. We efficiently fabricated an antibiotic enhancer Gm@UiO-66-MA to remove bacterial H2S and sensitize an antibacterial by modifying UiO-66-NH2 with maleic anhydride (MA) and then loading it with gentamicin (Gm). UiO-66-MA achieved the removal of bacterial endogenous H2S and the destruction of bacterial biofilm by selectively undergoing Michael addition with H2S. Moreover, Gm@UiO-66-MA further enhanced the susceptibility of tolerant E. coli to Gm after reducing bacterial intracellular H2S levels. An in vivo skin wound healing experiment confirmed that Gm@UiO-66-MA could greatly reduce the risk of bacterial reinfection and accelerate wound healing. Overall, Gm@UiO-66-MA offers a promising antibiotic sensitizer for minimizing bacterial resistance and a therapeutic strategy for tolerant bacteria-related refractory infections.

Utilization Of Antibiotics In Rural Communities Of Sub- Saharan Africa: Challenges And Resistances

In the last seven decades, antibiotics have greatly influenced the remarkable advancement in world health by becoming the standard therapy for infectious diseases. Antibiotic resistance (ABR) is a significant worldwide human health issue, having notably negative effects in low- and middle-income countries (LMICs). What were once fatal illnesses are now beaten by millions of people. But since there are only so many antibiotics available, misusing them has resulted in antibiotic resistance and decreased efficacy within a few years after the release of every lifesaving antibiotic. The WHO claims that the threat of antibiotic resistance to global health and development. The Sustainable Development Goals (SDGs) must be attained urgently through multi-sectoral approach. One of the ten leading worldwide public health hazards to civilization, according to WHO, is ABR. The major causes of the emergence of infections that are resistant to antibiotics are their improper usage and excessive use. The spread of bacteria, some of which may be antibiotic-resistant, is encouraged by a lack of safe drinking water, sanitation facilities, and effective infection control and prevention measures. Antibiotic resistance is as significant a threat to international security, food and nutrition security, and industrialization, according to the WHO, as terrorist attacks and global warming. ABR has a huge cost to the economy. Long-term disease not only increases the risk of mortality and incapacity but also lengthens hospital stay, necessitates the use of more expensive medications, and puts a strain on the finances of those affected. In the absence of powerful antibiotics, contemporary medicine's ability to cure infections, including those that arise following extensive surgeries and invasive procedures, would be compromised. Due to the lack of adequate mass surveillance, it is difficult to determine the scope of the ABR issue in LMICs, although considerable progress has been made in recent years since the WHO Global Antibiotic Resistance and Use Surveillance System (GLASS) initiative was launched in 2015. One of the main factors influencing the choice of ABR in LMICs is the widespread and frequently improper use of antibiotics in people, animals, and crops. This, combined with the insufficient control of pharmacological byproducts at the centers of manufacturing, must be quickly addressed. ABR spreads more quickly in LMICs because a number of factors including poor sanitation and hygiene insufficient exposure to sufficient health facilities, and a lack of legislation. The aim is to review to predisposing factors that influence the use of antibiotics aimed at informing policy decision on antibiotics use.