The cross-kingdom transmission of high-risk antibiotic resistance genes in compost-soil-plant systems and health risks assessment

Aquatic environments are identified as an ideal setting for acquisition and dissemination of antibiotic resistance, and human exposure to antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in aquatic environments may pose an additional health risk. Quantitative microbial risk assessment (QMRA) has been suggested as a suitable method to evaluate and quantify this health risk. However, information about the exposure to ARB and ARGs in aquatic environments is lacking for many scenarios and dose-response models regarding the ARB infections are not developed yet. This review summarizes the current knowledge regarding the ARB and ARGs in aquatic environments and highlights the challenging questions remaining to be answered to better forecast the health risks caused by ARB and ARGs in water environments. The questions include what are the missing information needed to quantify the human health risks caused by exposing to ARB and ARGs in aquatic environments? what are the suitable markers to evaluate the ARB/ARGs contamination in aquatic environments? how frequently do the ARG selection and propagation occur in aquatic environments? and are there any unknown hot spots? Studies on the above topics will contribute to better management of antibiotic resistance dissemination in water environments and its risks on human health.Abbreviations3GC3rd generation cephalosporinsARBAntibiotic resistant bacteriaARGAntibiotic resistance geneCFUColony forming unitDBPDisinfection by-productseDNAExtracellular DNAEPSExtracellular polymeric substancesHGTHorizontal gene transferISCRInsertion sequence common regionMARMultiple antibiotic resistantMICMinimum inhibitory concentrationMGEMobile genetic elementsMSWMunicipal solid wasteQMRAQuantitative microbial risk assessmentVBNCViable but non-culturableWWTPWastewater treatment plant

The air-borne antibiotic resistome: Occurrence, health risks, and future directions

The propagation of antibiotic resistance genes (ARGs) from domestic livestock manure is an unnegligible important environmental problem. There is an increasing need to understand the role of domestic livestock manure in causing antibiotic resistance in the environment to minimize risks to human health. Here, we targeted β-lactam resistance genes (bla genes), primarily discovered in clinical settings, to compare the high-risk ARG profile and their main spreading vectors of 26 family livestock farms in China and analyze the effects of domestic livestock manure on their receiving farmland environments. Results showed that the high-risk bla genes and their spreading carriers were widely prevalent in livestock and poultry manure from family farms. The blaampC gene encoding extended-spectrum AmpC β-lactamases, as well as its corresponding spreading carrier (class-1 integron), had the highest occurrence level. The bla gene abundance in family chicken farms was higher than that in family swine and cattle farms, while the bla gene contamination in the feces of laying hens or beef cattle was worse than that in corresponding broiler chickens or dairy cattle. Notably, the application from domestic livestock manure led to substantial emission of bla genes, which significantly increased the abundance of high-risk resistance genes in farmland soil by 12–46 times. This study demonstrated the prevalence and severity of high-risk resistance genes in domestic livestock and poultry manure; meanwhile, the discharge of bla genes also highlighted the need to mitigate the persistence and spread of these elevated high-risk genes in agricultural systems.

Antibiotic resistance in the Ganga River: Investigation of antibiotic resistant bacteria and antibiotic resistance genes, and public health risk assessment

Climate and nutrients regulate biographical patterns and health risks of antibiotic resistance genes in mangrove environment

Chlorine and UV combination sequence: Effects on antibiotic resistance control and health risks of ARGs.

A comprehensive framework of health risk assessment for antibiotic resistance in aquatic environments: Status, progress, and perspectives.

Waterborne disease is a global burden, which is mainly caused by waterborne pathogens disseminated through unsafe water, inadequate sanitation, and hygiene. Antibiotic resistance, which can also spread in water, has become an increasingly serious global health threat as it can prevent the effective treatment of infectious diseases. Improvements on water treatment and detection are the two critical strategies to control the surveillance of waterborne pathogens as well as antibiotic resistance bacteria and genes. The advancement in photo- and electro-chemical methods may provide more opportunities on decentralized water treatment and on-site pathogen monitoring under source-limited conditions. This thesis is dedicated to exploring the possible solutions to automatic, rapid, and easy-to-use in situ pathogen analysis for environmental water by adopting photo- or electro-chemical method, and to enhanced removal of antibiotic resistance bacteria (ARB) and antibiotic resistance genes (ARGs) from wastewater by combining photo- and electro-chemical techniques. These include removal of ARB and ARGs by UV-assisted electrochemical treatment, electrochemical cell lysis (ECL) for DNA extraction from bacteria, and sunlight-activated propidium monoazide (PMA) pretreatment for live/dead bacteria differentiation by quantitative real-time polymerase chain reaction (qPCR) detection. Both experimental approaches and computational modelling were used to evaluate the performance of the techniques and to bring more insights into the mechanism. Each study presents a demonstration on real environmental or wastewater to access the potential of their applications under complex environmental parameters. UV-assisted electrochemical treatment for ARB and ARGs was conducted using a blue TiO₂ nanotube array (BNTA) anode. The inactivation of tetracycline- and SMX-resistant E. coli and the corresponding plasmid coded genes (tetA and sul1) damage was measured by plate counting on selective agar and qPCR, respectively. As a comparison of UV treatment alone, the enhanced reduction of both ARB and ARGs was achieved by UV-assisted electrochemical oxidation (UV-EO) without Cl⁻ and was further facilitated with the presence of Cl⁻, which is attributed to the in-situ generated oxidants by electrochemical process. Significantly slower removal of ARG than ARB was observed for both UV irradiation alone and UV-EO treatment, wherein intracellular ARG generally reduced slower than extracellular ones, and short amplicons reduced significantly slower than long ones. The predominant nucleotide damage by UV irradiation and conformational change by UV-EO treatment was visualized by DNA gel electrophoresis for treated extracellular ARGs. The mechanism on ARB and ARGs damage was further understood by computational chemical modeling. The slower reduction was found for the native bacteria and genes, tetA and sul1, in the latrine wastewater than that in laboratory-prepared buffered samples. The result emphasizes that all the UV-based techniques may only apply after other treatments to avoid the impairment by the transmittance, color, and particulate material in environmental or wastewater. A comprehensive investigation was conducted for ECL in terms of its performance on DNA extraction from gram-negative bacteria (Escherichia coli and Salmonella Typhi) and gram-positive bacteria (Enterococcus durans and Bacillus subtilis). A milliliter-output ECL device was developed based on the disruption of the cell membrane by OH⁻ that can be generated locally at the cathode and accumulated improvingly through a cation exchange membrane. Both gram-negative and gram-positive bacteria were successfully lysed within 1 min at a low voltage of ~5 V. To better understand the pH effects on cell lysis, the pH profile at the cathode surface and in bulk cathodic effluent was simulated via hydroxide transport in the cathodic chamber. The demonstration of ECL on various environmental water sample types (including pond water, treated wastewater, and untreated wastewater) showed its potential as a prelude to nucleic-acid based analyses of waterborne bacteria in the field. Propidium monoazide (PMA), a nucleic acid-binding dye, has been used to distinguish live from dead cells prior to PCR-based detection. To explore the off-the-grid application of PMA, sunlight was investigated for PMA activation as an alternative light source to a typical halogen lamp. PMA was successfully activated by a solar simulator, and the pretreatment conditions were optimized with respect to the PMA concentration as 80 µM and the exposure time as 10 min. The optimal PMA pretreatment was tested on four different bacteria species (two gram-positive and two gram-negative), and the effects of sunlight intensity and multi-sequential treatment were studied. Sunlight-activated PMA pretreatment was eventually demonstrated on latrine wastewater samples with natural sunlight on both sunny and cloudy days. The results showed the potential of sunlight-activated PMA pretreatment to be integrated into a lab-on-a-chip (LOAC) PCR device for off-the-grid microbial detection and quantification.

One of the complex problems that many countries suffer from is how to deal with medical waste because of its harmful and devastating effects on humans and the environment. Hospitals around the world use and consume many different products. These products are composed of various materials, and many of them contain heavy metals in their production and manufacturing, which are ultimately emitted into the environment, posing a major danger and risk to human health. This work focused on assessing the contamination levels of medical waste ash after the incineration process. Ash samples were collected from major hospitals in the capital, Baghdad. The health risks resulting from heavy metal pollution were calculated. Medical waste ash was collected at different times from three major hospitals within the capital, Baghdad, and tested for contamination with heavy metals. To measure the bottom ash samples, X-ray spectroscopy (XRF) technology was used to determine heavy metal concentrations. The results showed the presence of more than twenty elements in the ash of medical waste, including the heavy metals found in Baghdad hospitals. Work was done on eight of these heavy metals due to their high concentrations. These selected elements are considered highly toxic and dangerous if exposed to them, including zinc (Zn), lead (Pb), arsenic (As), cobalt (Co), and copper. (Cu), nickel (Ni), chromium (Cr), and mercury (Hg). To evaluate the health risks of this pollution. All of these elements are a major problem if exposed to them. The amount of contamination was calculated using the contamination factor (CF). The results showed that the percentage of As, Cd, Hg, Zn, Pb, and Cu was very high. Meanwhile, the concentrations of Co and Ni were moderate values in medical waste ash. Adult health risks were calculated using the non-cancer health risk ratio (HL). The calculated values show values higher than the safe level in Imam Ali Central Hospital, indicating a potential high health risk. Meanwhile, other hospitals (Sheikh Zayed and Dhari Al Fayyad) recorded risk values below the safe level, indicating no health risks. The health risk assessment indicated that there are three main routes of human exposure: “ingestion, inhalation, and skin contact.” The cancer risk index (Risk) was also calculated. The values obtained were within the acceptable range. An analysis of the metal pollution index was also conducted, and it was found that heavy metals pose a non-cancerous risk. But the harmful effects of pollution from ash disposal have been particularly serious because they may contain high concentrations of heavy metals.

Preventive Medicine: A Ready Solution for a Health Care System in Crisis

Metagenomic investigation of antibiotic resistance genes and assessment of their health risk in antimony-mining area.

Urban environments are heavily influenced by various activities, leading to contamination of water sources by emerging contaminants (ECs). Among these, caffeine (CAF) and N, N-diethyl-meta-toluamide (DEET) are notable ECs frequently found in domestic sewage due to human activities. Despite extensive research on emerging contaminants, limited studies have focused on the seasonal variations, human health and ecological risks of CAF and DEET in urban groundwater, particularly in Indian cities. This study aimed to analyze the occurrence, spatial distribution, ecological and health risks of CAF and DEET in groundwater in Vellore city, Tamil Nadu, India. A total of 96 groundwater samples were collected across four seasons in 2022 and analyzed using Hichrom HPLC in an 844 UV/VIS compact Ion Chromatography system. CAF and DEET were detected in 95% and 96% of samples, with mean concentrations of 34μg/L and 30μg/L, respectively. Contamination levels were higher during the Southwest Monsoon (SWM) and Northeast Monsoon (NEM) seasons. Health risk assessments for children, women, and men showed that CAF posed significant risks, particularly to children during the NEM season, followed by women and men. Although DEET exhibited lower health risks overall, children remained the most vulnerable group. Statistical analysis confirmed significant differences in exposure levels, with children showing the highest variations. Ecological risk assessment revealed that 96.88% of samples containing CAF posed moderate ecological risks, while 6.25% of DEET samples fell into the same category. This study highlights the widespread presence of CAF and DEET in urban groundwater and their associated health and ecological risks. The findings emphasize the need for effective strategies to monitor and mitigate EC contamination in urban water systems.

INTRODUCTION: Genetic testing identifies patients with an increased risk for hereditary cancer and assists in development of clinical management or cancer prevention strategies. Utilization of multigene panels for patients with a personal or family history of cancer has the ability to identify a significant number of pathogenic variants in high risk and moderate risk genes. Importantly, at-risk patients with previously negative single gene testing can be retested with multigene panels. We characterized the mutations found in patients who had inherited cancer multi-gene panel testing, including patients with negative BRCA testing, and explored the phenotypes associated with the most prevalently mutated gene. METHODS: Patients were identified by a Community-Based Genetics Program and sent to a commercial laboratory for multi-gene panel testing. A retrospective query of multi-gene oncology tests was performed: patient history, family history and previous genetic test results were reported on the requisition. The following Genes were Utilized in the Inherited Cancer Panels: High risk genes (APC, BMPR1, BRCA1, BRCA2, CDH1, CDKN2A, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, TP53, VHL), moderate risk genes (ATM, CHEK2, PALB2), and genes with increase risk of unknown magnitude (AXIN2, BARD1, BRIP1, CDK4, FANCC, NBN, RAD51C, RAD51D, XRCC2). The combination of genes analyzed was depends on the panel ordered. RESULTES: 529 individuals were tested with 38 individuals with pathogenic variant (PV) or variant expected to be pathogenic (VEP). Of the 529 individuals, 154 (29%) had previous testing and 12 (7.8%) had PV/VEP. Interestingly, 48% of PV/VEP were in the moderate risk genes ATM, PALB2, CHEK2, and CHEK2 being the most commonly mutated gene. The following table details the genes with Positive and VEP Results: Table 1: Gene Distribution Patients with PV/VEPGeneN%CHEK21333.3BRCA2512.8BRCA1410.2MUTYH512.8PALB2410.2ATM25.13RAD51C12..56MLH112.56MSH212.56MSH612.56PTEN12.56BRIP112.56 The majority of patients with CHEK2 mutations had a personal history of breast cancer (69%), but the family histories exhibited varied phenotypic expression. Personal and Family History for Patients with CHEK2 PV/VEP or VUS (N=26)SitePersoanl historyFamily historyBreast1819Uterine11Ovarian16Colon 9Lung 1Pancreatic 3Gastric 2Renal 2Lymphoma 4Brain 2Skin 2Esophageal 1Prostate 6Thyroid 2Gynecologic 1 CONCLUSION: Inherited cancer panels provide patients with genetic information that would otherwise be missed by single gene testing and provides access to risk assessment and medical management. Using multigene panels, PV/VEP were discovered in 7.8% of patients with previous negative BRCA testing. CHEK2, a moderate risk gene, was identified in 33% of patients with a PV/VEP. The phenotypic expression for CHEK2 is primarily breast cancer with a wide spectrum of solid and hematological tumors. Citation Format: Daib S, Sedlacek S, Hamlington B, Brzeskiewicz L, Goetsch B, Tedesco K, Patel G, Sudhoff K, Mullineaux L, Langer L. The performance of next generation panel testing in individuals assessed by a community-based genetics program. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-19.

Introduction:The global health threat posed by the ongoing deterioration in natural ecosystems and damage to our physical environment is growing at a rapid pace. Less recognized is the threat from natural hazard disasters, which concentrate contaminants from the damaged environment and expose large vulnerable populations to life-threatening medical conditions and disease. Currently neither international nor any national health and medical emergency response protocols or programs have prepared health responses to protect the health of communities in such events.Aim:This study performed a retrospective health risk assessment on two recent events where such impacts unfolded, namely the 2015 southeast Equatorial Asia smoke haze disaster and the 2016 Melbourne thunderstorm asthma epidemic. The primary objective was to test if the characterization of health risk could have been identified earlier and catastrophic levels of mortality and morbidity reduced.Methods:The study employed a two-staged retrospective health risk characterization assessment. The first step applied the UNISDR (2017) framework for health risk disaster assessment combing a thematic and targeted word literature review to identify the level of health and medical risk knowledge prior to each event. The second stage applied a risk characterization matrix developed using ISO and Australian Health Department semi-quantitative health assessment standards.Results:The 2015 southeast Equatorial Asia smoke haze disaster risk assessment was characterized as an extreme health risk and the 2016 Melbourne thunderstorm asthma epidemic characterized as a high health risk.Discussion:Innovative medical response approaches are urgently needed to mitigate the growing health risk to whole populations from natural hazard disasters compounded by deteriorating natural ecosystems and the physical environment. This requires emergency medical and health teams to recognize the two-tailed human health risk from natural disaster hazards, along with investment in advanced planning, environmental risk surveillance, specialist training, technical guidance, and multi-sector coordination.

Antibiotic resistance genes and virulence factors in the plastisphere in wastewater treatment plant effluent: Health risk quantification and driving mechanism interpretation