Global Spread Of Antibiotic Resistance Research Articles

Evaluation of LPRDA Pentapeptide for the Prevention and Treatment of Staphylococcus aureus Peritoneal Infection

Targeting virulence determinants is a promising approach to controlling S. aureus infections in the face of the global spread of antibiotic resistance. S. aureus-induced peritonitis often occurs in dialysis, implant and trauma patients. To develop novel prevention and treatment options for peritoneal infection, we investigated the oligopeptide sortase A inhibitor LPRDA as a non-conventional antibacterial that does not affect staphylococcal survival. Administration of LPRDA prior to S. aureus challenge reduced the bacterial load of internal organs and bacterial colonization of the abdominal cavity in animals. In addition, LPRDA inhibited α-hemolysin production in 80% of the 35 reference and clinical S. aureus strains tested. Consequent research of LPRDA interactions with cefazolin and vancomycin has demonstrated the potential for combined application of the antivirulent and antibiotic agents under study.

Assessment of chlorine and hydrogen peroxide on airborne bacteria: Disinfection efficiency and induction of antibiotic resistance

Airborne pathogens severely threaten public health worldwide. Air disinfection is essential to ensure public health. However, excessive use of disinfectants may endanger environmental and ecological security due to the residual disinfectants and their by-products. This study systematically evaluated disinfection efficiency, induction of multidrug resistance, and the underlying mechanisms of disinfectants (NaClO and H2O2) on airborne bacteria. The results showed that airborne bacteria were effectively inactivated by atomized NaClO (>160 μg/L) and H2O2 (>320 μg/L) after 15 min. However, some bacteria still survived after disinfection by atomized NaClO (0–80 μg/L) and H2O2 (0–160 μg/L), and they exhibited significant increases in antibiotic resistance. The whole-genome sequencing of the resistant bacteria revealed distinct mutations that were responsible for both antibiotic resistance and virulence. This study also provided evidences and insights into possible mechanisms underlying the induction of antibiotic resistance by air disinfection, which involved intracellular reactive oxygen species formation, oxidative stress responses, alterations in bacterial membranes, activation of efflux pumps, and the thickening of biofilms. The present results also shed light on the role of air disinfection in inducing antibiotic resistance, which could be a crucial factor contributing to the global spread of antibiotic resistance through the air.

Traveller studies in low- and middle-income countries: a critical gap in global antibiotic resistance surveillance.

A substantial proportion of global travel occurs between low- and middle-income countries (LMICs) for the purposes of migration, medical tourism, trade and employment, and this is likely to accelerate due to climate-change-related migration. Traveller studies based in LMICs are needed to better monitor the global spread of antibiotic resistance.

Large-Scale Biogeographical Shifts of Abundance of Antibiotic Resistance Genes and Marine Bacterial Communities as Their Carriers along a Trophic Gradient.

The role of marine environments in the global spread of antibiotic resistance still remains poorly understood, leaving gaps in the One Health-based research framework. Antibiotic resistance genes (ARGs) encoding resistance to five major antibiotic classes, including sulfonamides (sul1, sul2), tetracyclines (tetA, tetB), β-lactams (blaCTX-M, blaTEMblaVIM), macrolides (ermB, mphA), aminoglycosides (aac3-2), and integrase gene (intl1) were quantified by RT-qPCR, and their distribution was investigated in relation to environmental parameters and the total bacterial community in bottom layer and surface waters of the central Adriatic (Mediterranean), over a 68 km line from the wastewater-impacted estuary to coastal and pristine open sea. Seasonal changes (higher in winter) were observed for antibiotic resistance frequency and the relative abundances of ARGs, which were generally higher in eutrophic coastal areas. In particular, intl1, followed by blaTEM and blaVIM, were strongly associated with anthropogenic influence and Gammaproteobacteria as their predominant carriers. Water column stratification and geographic location had a significant influence on ARGs distribution in the oligotrophic zone, where the bacterial community exhibited a seasonal shift from Gammaproteobacteria in winter to Marine group II in summer.

Plasmid‐Mediated Co‐Occurrence of mcr-1.1 in Extended‐Spectrum β‐Lactamase (ESBL)‐Producing Escherichia coli Isolated From the Indigenous Seminomadic Community in Malaysia

The growing prevalence of commensal antibiotic resistant Escherichia coli poses a significant concern for the global spread of antibiotic resistance. Stool samples (n = 35) from a seminomadic indigenous community in Malaysia, the Jehai, were screened for multidrug‐resistant bacteria, specifically the extended‐spectrum β‐lactamase (ESBL) producers. Subsequently, whole‐genome sequencing was used to provide genomic insights into eight ESBL‐producing E. coli that colonised eight individuals. The ESBL E. coli isolates carry resistance genes from various antibiotic classes such as the β‐lactams (blaTEM, blaCTX-M−15 and blaCTX-M−55), quinolones (gyrA, qnrS and qnrS1) and aminoglycosides (aph(3′)-Ia, aph(6)-Id and aac(3)-IId). Three concerning convergence of ESBL, colistin and metal resistance determinants, with three plasmids from H‐type lineage harbouring blaCTX-M and mcr-1.1 genes were identified. Using the Oxford Nanopore Technology (ONT) Native Barcoding Kit (SQK‐NBD114.24) in conjunction with the R10.4.1 flow cell, which achieved an average read accuracy (Q > 10) of 99.84%, we further characterised the mcr-1.1‐bearing plasmids, ranging in size from 25 to 28 kb, from three strains of E. coli. This report represents the first whole genome analysis of multidrug‐resistant bacteria, specifically those resistant to colistin, found within the indigenous population in Malaysia. It strongly indicates that the pertinent issue of colistin resistance in the country is far more significant than previously estimated.

Bioengineering the Antimicrobial Activity of Yeast by Recombinant Thanatin Production.

The global spread of antibiotic resistance marks the end of the era of conventional antibiotics. Mankind desires new molecular tools to fight pathogenic bacteria. In this regard, the development of new antimicrobials based on antimicrobial peptides (AMPs) is again of particular interest. AMPs have various mechanisms of action on bacterial cells. Moreover, AMPs have been reported to be efficient in preclinical studies, demonstrating a low level of resistance formation. Thanatin is a small, beta-hairpin antimicrobial peptide with a bacterial-specific mode of action, predetermining its low cytotoxicity toward eukaryotic cells. This makes thanatin an exceptional candidate for new antibiotic development. Here, a microorganism was bioengineered to produce an antimicrobial agent, providing novel opportunities in antibiotic research through the directed creation of biocontrol agents. The constitutive heterologous production of recombinant thanatin (rThan) in the yeast Pichia pastoris endows the latter with antibacterial properties. Optimized expression and purification conditions enable a high production level, yielding up to 20 mg/L of rThan from the culture medium. rThan shows a wide spectrum of activity against pathogenic bacteria, similarly to its chemically synthesized analogue. The designed approach provides new avenues for AMP engineering and creating live biocontrol agents to fight antibiotic resistance.

Integration of water, sanitation, and hygiene program with biosecurity: A One Health approach to reduce the prevalence and exposure of antibiotic-resistant bacteria in the livestock community

The global spread of antibiotic resistance poses a significant threat to public health and is one of the main causes of this problem. Livestock farming plays a significant role in the horizontal and vertical transmission of treatment-resistant genes and bacteria. These processes involve contact with agricultural products and the environment, raising concerns for public health, and farming communities. The farming community is composed of a staggering 608 million farms worldwide, and their livelihood depends heavily on livestock farming. To address this issue, a multidisciplinary One Health approach focusing on integrated monitoring and intervention for humans, animals, and the environment is essential. Water, sanitation, and hygiene (WaSH) programs have the potential to significantly reduce the risk of exposure to antibiotic-resistant bacteria, particularly extended spectrum beta-lactamase (ESBL) Escherichia coli, by obstructing the transmission route between humans and animals. Additional risk reduction measures for ESBL E. coli infection in animals include vaccination and biosecurity program implementation. Water, sanitation, and hygiene and biosecurity measures must be combined to maximize the effectiveness of the One Health program. Therefore, this study aimed to describe recent advances in biosecurity and WaSH interventions in the livestock environment, analyze the effects of these interventions on human and animal health, and investigate potential future scenarios within the quantitative microbial risk assessment framework. This study used an integrative literature review through searches of four databases, a review of World Health Organization documents through websites, and an examination of relevant texts from previously obtained reference lists. Although hygiene and sanitation are often combined, there is still a lack of quantitative evaluation of the efficacy of integrating WaSH with biosecurity in livestock. In addition, the integration of the WaSH program with biosecurity has potential as a One Health intervention in the coming years. Keywords: antibiotic-resistant bacteria, biosecurity, extended-spectrum beta-lactamase Escherichia coli, One Health, scenario, water, sanitation, and hygiene.

Therapeutic Potential and Prospects of Application of Peptides in the Era of the Global Spread of Antibiotic Resistance

Therapeutic Potential and Prospects of Application of Peptides in the Era of the Global Spread of Antibiotic Resistance

Therapeutic Potential and Application Prospects of Antimicrobial Peptides in the Era of Global Spread of Antibiotic Resistance

In the era of the growing global threat of antibiotic resistance, antimicrobial peptides (AMPs) are considered as new generation drugs for treatment of various infectious diseases. In this review, AMPs are seen as an alternative to traditional antibiotics, many of which have already lost or are gradually reducing their effectiveness against a number of critically important pathogenic microorganisms. Recent outbreaks of secondary infections during the COVID-19 pandemic have increased the interest in AMPs due to an acute shortage of effective agents against bacterial and fungal infections. The review summarized current data on clinical studies of AMPs, assembled a list of developed drugs based on AMPs at various stages of clinical trials, highlighted the urgency of study of new AMPs, and systematized the most relevant clinical data and application of AMPs.

Antibiotic Use in Pregnancy: A Global Survey on Antibiotic Prescription Practices in Antenatal Care.

Antibiotic prescription and use practices in the antenatal care setting varies across countries and populations and has the potential to significantly contribute to the global spread of antibiotic resistance. This study aims to explore how healthcare practitioners make decisions about antibiotic prescriptions for pregnant women and what factors play a role in this process. A cross-sectional exploratory survey consisting of 23 questions, including 4 free-text and 19 multiple-choice questions, was distributed online. Quantitative data were collected through multiple-choice questions and was used to identify the most common infections diagnosed and the type of antibiotics prescribed. Qualitative data were gathered through free-text answers to identify gaps, challenges, and suggestions, and the data were analyzed using thematic analysis. A total of 137 complete surveys mostly from gynecologists/obstetricians from 22 different countries were included in the analysis. Overall, national and international clinical guidelines and hospital guidelines/protocols were the most frequently used sources of information. This study highlights the crucial role of laboratory results and guidelines at different levels and emphasizes region-specific challenges and recommendations. These findings underscore the pressing need for tailored interventions to support antibiotic prescribers in their decision-making practice and to address emerging resistance.

Advantages of long- and short-reads sequencing for the hybrid investigation of the Mycobacterium tuberculosis genome.

In the fight to limit the global spread of antibiotic resistance, computational challenges associated with sequencing technology can impact the accuracy of downstream analysis, including drug resistance identification, transmission, and genome resolution. About 10% of Mycobacterium tuberculosis (MTB) genome is constituted by the PE/PPE family, a GC-rich repetitive genome region. Although sequencing using short read technology is widely used, it is well recognized its limit in the PE/PPE regions due to the unambiguously mapping process onto the reference genome. The aim of this study was to compare the performances of short-reads (SRS), long-reads (LRS) and hybrid-reads (HYBR) based analysis over different common investigative tasks: genome coverage estimation, variant calling and cluster analysis, drug resistance detection and de novo assembly. For the study 13 model MTB clinical isolates were sequenced with both SRS and LRS. HYBR were produced correcting the long reads with the short reads. The fastq from the three approaches were then processed using a customized version of MTBseq for genome coverage estimation and variant calling and using two different assemblers for de novo assembly evaluation. Estimation of genome coverage performances showed lower 8X breadth coverage for SRS respect to LRS and HYBR: considering the PE/PPE genes, SRS showed low results for the PE_PGRS family, while obtained acceptable coverage in PE and PPE genes; LRS and HYBR reached optimal coverages in PE/PPE genes. For variant calling HYBR showed the highest resolution, detecting the highest percentage of uniquely identified mutations compared to LRS and SRS. All three approaches agreed on the identification of two major clusters, with HYBR identifying an higher number of SNPs between the two clusters. Comparing the quality of the assemblies, HYBR and LRS obtained better results than SRS. In conclusion, depending on the aim of the investigation, both SRS and LRS present complementary advantages and limitations implying that for a full resolution of MTB genomes, where all the mentioned analyses and both technologies are needed, the use of the HYBR approach represents a valid option and a well-rounded strategy.

Time-course biofilm formation and presence of antibiotic resistance genes on everyday plastic items deployed in river waters.

The plastisphere has been widely studied in the oceans; however, there is little information on how living organisms interact with the plastisphere in freshwater ecosystems, and particularly on how this interaction changes over time. We have characterized, over one year, the evolution of the eukaryotic and bacterial communities colonizing four everyday plastic items deployed in two sites of the same river with different anthropogenic impact. α-diversity analyses showed that site had a significant role in bacterial and eukaryotic diversity, with the most impacted site having higher values of the Shannon diversity index. β-diversity analyses showed that site explained most of the sample variation followed by substrate type (i.e., plastic item) and time since first colonization. In this regard, core microbiomes/biomes in each plastic at 1, 3, 6 and 12 months could be identified at genus level, giving a global overview of the evolution of the plastisphere over time. The measured concentration of antibiotics in the river water positively correlated with the abundance of antibiotic resistance genes (ARGs) on the plastics. These results provide relevant information on the temporal dynamics of the plastisphere in freshwater ecosystems and emphasize the potential contribution of plastic items to the global spread of antibiotic resistance.

Emergent crisis of antibiotic resistance: A silent pandemic threat to 21st century.

Antibiotic resistance has become an indispensably alarming menace to the global community. The primary factors are overuse and abuse of antibiotics, lack of novel medicines under development, the health care industry's focus on profit, and the absence of diagnostic testing prior to the prescription of antibiotics. Additionally, over the past few decades, the main factors contributing to the global spread of antibiotic resistance have been the overuse of antibiotics in livestock and other animals, drug efficacy, development of fewer new vaccines, environmental toxicity, transmission through travel, and lack of funding for healthcare research and development. These factors have accelerated resistance in microorganisms through structural and functional modifications in bacteria such as reduced drug permeability, increased efflux pumps, enzymatic antibiotic modification, and change in drug target, intracellular infection, and biofilm creation. There has been an increase in resistance during the pandemic and among cancer patients due to improper prescriptions. A number of modern therapeutic alternatives have been developed to curb widespread antibiotic resistance such as nanoparticle, bacteriophage, and antimicrobial biochemical approaches. It is high time to explore new alternatives to curtail enormous increase in resistant pathogens which could be an incurable global confrontation. This review highlights the complete insight on the global drivers of resistance along with the modes of action and impacts, finally discussing the latest therapeutic alternatives.

Use of Vitex doniana (black plum) and Abutilon hirtum (Florida keys) extracts as an integral part of phytomedicine in tackling multidrug-resistant Salmonella.

The high prevalence and global spread of antibiotic resistance is driving the search for new antibacterial agents. Screening small molecules against specific bacterial targets has not yielded new compounds therefore functional assays and phenotypic screens are now being used. In Nigeria, drug resistance towards Salmonella is a major public health concern. Nine fully characterized clinical Salmonella isolates, from the Department of Medical Microbiology, Jos University Teaching Hospital, Plateau State, Nigeria, were screened by broth microdilution for susceptibility to fractionated ethanol extracts of Vitex doniana and Abutilon hirtum. This was compared to the control organism ATCC25922 and a range antibiotics: CH (chloramphenicol), SP (sparfloxacin), AM (amoxicillin), CN (gentamicin), S (streptomycin), PEF (pefloxacin). The most common resistance profile was AM,CN,S with most isolates susceptible to fluoroquinolones. Activity was detected from both plant extracts with MICs of extracted fractions ranging from 150 - 300 µg/mL. Interestingly both plants produced extracts with bactericidal activity from 300 - 600 µg/mL. V. doniana exhibited better activity against the resistant Salmonella strains in terms of greater inhibition zones, but A. hirtum extracts were more consistently active against all isolates. In comparison with the synthetic drugs, both plant extracts exhibited activity against more isolates - this activity was bactericidal. Nigeria needs better anti-salmonella products and these results represent a starting point for antibiotic drug discovery.

The Impact of Pre- and Probiotic Product Combinations on Ex vivo Growth of Avian Pathogenic Escherichia coli and Salmonella Enteritidis

Due to the global spread of antibiotic resistance, there is a strong demand to replace antimicrobial growth promotors in livestock. To identify suitable additives that inhibit the growth of avian pathogenic Escherichia coli O1/O18 and Salmonella enterica serotype Enteritidis strains, an ex vivo screening was performed. Inulin and fructooligosaccharides (FOS) were investigated as prebiotics. Enterococcus faecium and Bacillus coagulans served as probiotic strains. Firstly, the pathogen was anaerobically incubated in caecal digesta from different broiler breeder flocks with the addition of feed additives. Secondly, subsamples of these suspensions were incubated in an antibiotic medium for selective growth of the pathogen. During this step, turbidity was recorded, and lag times were calculated for each pathogen as readout of growth inhibition. Combinations of E. faecium with inulin or FOS significantly extended the lag time for E. coli compared to control. Moreover, older age was a significant factor to enhance this inhibitory effect. In contrast, the combination of FOS and B. coagulans showed shorter lag times for S. Enteritidis. Our results indicate that the E. faecium strain with prebiotics may inhibit the pathogen proliferation in the studied poultry flocks. Furthermore, our results suggest that prophylactic treatments should be assigned by feed additive, age and animal origin.

New perspectives on mobile genetic elements: a paradigm shift for managing the antibiotic resistance crisis.

Mobile genetic elements (MGEs) are primary facilitators in the global spread of antibiotic resistance. Here, we present novel ecological and evolutionary perspectives to understand and manage these elements: as selfish entities that exhibit biological individuality, as pollutants that replicate and as invasive species that thrive under human impact. Importantly, each viewpoint suggests new means to control their activity and spread. When seen as biological individuals, MGEs can be regarded as therapeutic targets in their own right. We highlight promising conjugation-inhibiting compounds that could be administered alongside antibiotic treatment. Viewed as pollutants, sewage treatment methods could be modified to efficiently remove antimicrobials and the resistance genes that they select. Finally, by recognizing the invasive characteristics of MGEs, we might apply strategies developed for the management of invasive species. These include environmental restoration to reduce antimicrobial selection, early detection to help inform appropriate antibiotic usage, and biocontrol strategies that target MGEs, constituting precision antimicrobials. These actions, which embody the One Health approach, target different characteristics of MGEs that are pertinent at the cellular, community, landscape and global levels. The strategies could act on multiple fronts and, together, might provide a more fruitful means to combat the global resistance crisis.This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.

A new insight into the ARG association with antibiotics and non-antibiotic agents—antibiotic resistance and toxicity

Although concerns have been raised about co-selection for antibiotic resistance and various antibiotics and non-antibiotic agents, the data on their association in urban sludge is still limited. In addition, antibiotic contamination can result in not only the toxicity but also the antibiotic resistance. In this study, the first large-scale identification of antibiotics and non-antibiotic agents concern for co-selection of resistance against antibiotics was conducted in urban sludge. Co-occurrence analysis showed that antibiotic resistance genes (ARGs) had no significant correlation with the corresponding antibiotics. Therefore, the results of co-occurrence analysis based on antibiotic concentration and ARG abundance were always ambiguous and difficult to interpret. However, antibiotic resistance was positively correlated with highly toxic compounds such as diclofenac, enrofloxacin and nicotine, suggesting that environmental contaminants might influence antibiotic resistance while exerting toxicity through mechanisms such as changes in microbial community and enzyme activity. The close correlation between class 1 integrase gene (intI1) and diclofenac/enrofloxacin indicated that the co-selection scenario between environmental contaminants and ARGs was likely mediated via intI1. In total, the derived co-occurrence patterns improve our understanding of the co-selection between ARGs, antibiotics and non-antibiotic agents, and also reaffirm the importance of potential role of non-antibiotic agents in the global spread of antibiotic resistance.

Seasonal disparities and source tracking of airborne antibiotic resistance genes in Handan, China

The transmission of airborne antibiotic resistance genes (ARGs) loaded on particle is a significant global public health concern. Up to date, the dispersal pattern of airborne ARGs remains unclear despite their critical role in multiregional transmission. In this study, airborne ARGs loaded on fine particulate matter (PM2.5) and source tracking based on the airflow trajectories were performed by the potential source contribution function (PSCF) and concentration weighted trajectory (CWT) model. The results show that the absolute abundance of ARG subtypes were generally twice times higher in the winter season than that in the summer season, which could be attributable to winter haze events with high particulate matter concentrations in Handan. Exogenous input from serious haze events and local release of ARGs loaded on PM2.5 of air masses may cause higher levels of ARGs in the winter. Moreover, based on the positive correlation between the abundance of ARGs and PM2.5 concentration, a source tracing model of airborne ARGs was proposed to the estimate of ARGs release and dissemination. This study highlights airborne ARGs transmission loaded on PM2.5 of air masses, which facilitating the global spread of antibiotic resistance.

Synergistic effect of antimicrobial peptide LL-37 and colistin combination against multidrug-resistant Escherichia coli isolates.

Overview: The global spread of antibiotic resistance represents a serious threat for public health. Aim: We evaluated the efficacy of the antimicrobial peptide LL-37 as antimicrobial agent against multidrug-resistant Escherichia coli. Results: LL-37 showed good activity against mcr-1 carrying, extended spectrum β-lactamase- and carbapenemase-producing E. coli (minimum inhibitory concentration, MIC, from 16 to 64mg/l). Checkerboard assays demonstrated synergistic effect of LL-37/colistin combination against all tested strains, further confirmed by time-kill and post antibiotic effect assays. MIC and sub-MIC concentrations of LL-37 were able to reduce biofilm formation. Conclusion: Our preliminary data indicated that LL-37/colistin combination was effective against multidrug-resistant E. coli strains and suggested a new possible clinical application.

Critical evaluation of short, long, and hybrid assembly for contextual analysis of antibiotic resistance genes in complex environmental metagenomes

In the fight to limit the global spread of antibiotic resistance, the assembly of environmental metagenomes has the potential to provide rich contextual information (e.g., taxonomic hosts, carriage on mobile genetic elements) about antibiotic resistance genes (ARG) in the environment. However, computational challenges associated with assembly can impact the accuracy of downstream analyses. This work critically evaluates the impact of assembly leveraging short reads, nanopore MinION long-reads, and a combination of the two (hybrid) on ARG contextualization for ten environmental metagenomes using seven prominent assemblers (IDBA-UD, MEGAHIT, Canu, Flye, Opera-MS, metaSpades and HybridSpades). While short-read and hybrid assemblies produced similar patterns of ARG contextualization, raw or assembled long nanopore reads produced distinct patterns. Based on an in-silico spike-in experiment using real and simulated reads, we show that low to intermediate coverage species are more likely to be incorporated into chimeric contigs across all assemblers and sequencing technologies, while more abundant species produce assemblies with a greater frequency of inversions and insertion/deletions (indels). In sum, our analyses support hybrid assembly as a valuable technique for boosting the reliability and accuracy of assembly-based analyses of ARGs and neighboring genes at environmentally-relevant coverages, provided that sufficient short-read sequencing depth is achieved.