Biology subjects

Sutradhar, I.

Publications and source records attributed to Sutradhar, I..

4 recordsLinked to original sources

bioRxiv2023

Metal Ions and their Effects on Antimicrobial Resistance Development in Wastewater

Antimicrobial resistance (AMR) is a global health challenge and there is increasing recognition of the role of the environment, particularly wastewater, in the development and spread of AMR. Although trace metals are common contaminants in wastewater, the quantitative effects of trace metals on AMR in wastewater settings remain understudied. We experimentally determined the interactions between common antibiotic residues and metal ions found in wastewater and investigated their effects on the development of antibiotic resistance in Escherichia coli over time. These data were then used to expand on a previously developed computational model of antibiotic resistance development in continuous flow settings to incorporate the effects of trace metals acting in combination with multiple antibiotic residues. We found that the common metal ions, copper and iron, interact with both ciprofloxacin and doxycycline at wastewater relevant concentrations. This can significantly affect resistance development due to antibiotic chelation of the metal ions causing a reduction in the antibiotics bioactivity. Furthermore, modeling the effect of these interactions in wastewater systems showed the potential for metal ions in wastewater to significantly increase the development of antibiotic resistant E. coli populations. These results demonstrate the need to quantitatively understand the effects of trace metal-antibiotic interactions on AMR development in wastewater.

bioengineering↗

bioRxiv2023

Impact of Zinc Pre-exposure on de novo Antibiotic Resistance Development

Antimicrobial resistance (AMR) is a global health crisis that is currently predicted to worsen. While the impact of improper antibiotics is an established driver, much less is known on the impacts of metal supplements. Here, we specifically probe the impact of zinc (Zn) on AMR. In conflict settings where diarrhea disease cases are high, Zn is both given as a supplement for treatment of these diseases prior to use of antibiotics such as ciprofloxacin and is associated with weapons of war. In this study, we find that the order with which E. coli is exposed to zinc impacts resistance development, with increasing pre-exposure time leading to accelerated ciprofloxacin resistance, while combined exposure of zinc with ciprofloxacin delays ciprofloxacin resistance. We did not find evidence that zinc pre-exposure leads to genetic changes or change in antibiotic tolerance, though it does increase both the lag phase and doubling time of E. coli, suggesting the mechanism may be due to changes in gene expression. While the zinc phenotype behavior is not permeant and would no longer be observed if ciprofloxacin exposure did not occur right after zinc pre-exposure, the elevated MIC phenotype resulting from the zinc pre-exposure was more stable than the zinc phenotype. These results are important as they highlight the need to reexamine the clinical role of zinc in treating diarrheal diseases and assess if changes in resistance development observed in vitro are also observed in vivo. ImportanceAntimicrobial resistance (AMR) is a global problem. According to a 2014 Review on Antimicrobial Resistance, it is projected to result in several million deaths by 2050 (Review on Antimicrobial Resistance, Tackling a Crisis for the Health and Wealth of Nations, 2014). While the improper usage of antibiotic treatments is an accepted driver of AMR, little work has focused on how non-antibiotic medication, such as supplements, might impact this when combined with antibiotics. One supplement of interest is the heavy metal zinc which is used in conjunction with ciprofloxacin to treat diarrheal diseases in children. We find that the order and duration of zinc exposure has significant impact on resistance development. More specifically, although the combined presence of zinc and ciprofloxacin delays the onset of resistance, when used successively as they often are in practice, zinc pre-exposure followed by ciprofloxacin exposure results in faster resistance development.

microbiology↗

bioRxiv2023

Effects of Antibiotic Interaction on Antimicrobial Resistance Development in Wastewater

While wastewater is understood to be a critically important reservoir of antimicrobial resistance due to the presence of multiple antibiotic residues from industrial and agricultural runoff, there is little known about the effects of antibiotic interactions in the wastewater on the development of resistance. We worked to fill this gap in quantitative understanding of antibiotic interaction in constant flow environments by experimentally monitoring E. coli populations under subinhibitory concentrations of combinations of antibiotics with synergistic, antagonistic, and additive interactions. We then used these results to expand our previously developed computational model to account for the complex effects of antibiotic interaction. We found that while E. coli populations grown in additively interacting antibiotic combinations grew predictably according to the previously developed model, those populations grown under synergistic and antagonistic antibiotic conditions exhibited significant differences from predicted behavior. E. coli populations grown in the condition with synergistically interacting antibiotics developed less resistance than predicted, indicating that synergistic antibiotics may have a suppressive effect on antimicrobial resistance development. Furthermore E. coli populations grown in the condition with antagonistically interacting antibiotics showed an antibiotic ratio-dependent development of resistance, suggesting that not only antibiotic interaction, but relative concentration is important in predicting resistance development. These results provide critical insight for quantitatively understanding the effects of antibiotic interactions in wastewater and provide a basis for future studies in modelling resistance in these environments. ImportanceAntimicrobial resistance (AMR) is a growing global threat to public health expected to impact 10 million people by 2050, driving mortality rates globally and with a disproportionate effect on low- and middle-income countries. Communities in proximity to wastewater settings and environmentally contaminated surroundings are at particular risk due to resistance stemming from antibiotic residues from industrial and agricultural runoff. Currently, there is a limited quantitative and mechanistic understanding of the evolution of AMR in response to multiple interacting antibiotic residues in constant flow environments. Using an integrated computational and experimental methods, we find that interactions between antibiotic residues significantly affect the development of resistant bacterial populations.

bioengineering↗

bioRxiv2020

Computational Model to Quantify the Growth of Antibiotic Resistant Bacteria in Wastewater

Although wastewater and sewage systems are known to be significant reservoirs of antibiotic resistant bacterial populations and periodic outbreaks of drug resistant infection, there is little quantitative understanding of the drivers behind resistant population growth in these settings. In order to fill this gap in quantitative understanding of the development of antibiotic resistant infections in wastewater, we have developed a mathematical model synthesizing many known drivers of antibiotic resistance in these settings to help predict the growth of resistant populations in different environmental scenarios. A number of these drivers of drug resistant infection outbreak including antibiotic residue concentration, antibiotic interaction, chromosomal mutation and horizontal gene transfer, have not previously been integrated into a single computational model. We validated the outputs of the model with quantitative studies conducted on the eVOLVER continuous culture platform. Our integrated model shows that low levels of antibiotic residues present in wastewater can lead to increased development of resistant populations, and the dominant mechanism of resistance acquisition in these populations is horizontal gene transfer rather than acquisition of chromosomal mutations. Additionally, we found that synergistic antibiotic interactions lead to increased resistant population growth. These findings, consistent with recent experimental and field studies, provide new quantitative knowledge on the evolution of antibiotic resistant bacterial reservoirs, and the model developed herein can be adapted for use as a prediction tool in public health policy making, particularly in low income settings where water sanitation issues remain widespread and disease outbreaks continue to undermine public health efforts. ImportanceThe rate at which antimicrobial resistance (AMR) has developed and spread throughout the world has increased in recent years, and according to the Review on Antimicrobial Resistance in 2014 it is suggested that the current rate will lead several million people AMR-related deaths by 205025. One major reservoir of resistant bacterial populations that has been linked to outbreaks of drug resistant bacterial infections, but is not well understood, is in wastewater settings, where antibiotic pollution is often present. Using ordinary differential equations incorporating several known drivers of resistance in wastewater, we find that interactions between antibiotic residues and horizontal gene transfer significantly affect the growth of resistant bacterial reservoirs.

bioengineering↗