Before Alexander Fleming discovered penicillin, most common infections were fatal. Now, we have an armoury of drugs against almost all kinds of bacteria. But our wanton use of antibiotics has made these pesky creatures immune to drugs. Unrestricted consumption of antibiotics is only one reason for drug resistance. A new study by scientists at the Indian Institute of Technology, Delhi, shows that improper sewage treatment practices can escalate this menace.
Only about 40% of the sewage generated in Delhi is treated before being dumped into the Yamuna. But most plants do not disinfect the effluents before they are discharged. While this inadequate processing of sewage removes most organic pollutants, it breeds antibiotic resistance. Samples from sewage treatment plants in Delhi show large amounts of antibiotic-resistant bacteria in both the raw influents and the treated discharge. Even after treatment, the levels of these drug-resistant bacteria continued to be higher than levels considered safe for bathing.
“Bacteria develop drug resistance when they are repeatedly exposed to antibiotics. A similar condition is created in our guts when we eat antibiotics for every infection without completing its course,” Ziauddin Ahammad, the chief investigator of this study, explained for The Wire. This makes diseases harder to treat.
Worry over faeces load
In India, drug resistance is spurred by irrational prescription of antibiotics for even diseases like flu. Those bacteria that manage to adapt to antibiotics are released in the faeces and collected as sewage. Yet, there is a dearth of research that sheds light on what happens to the drug-resistant bacteria after they enter the environment.
To assess the current treatment strategies in neutralising what Ahammad calls an emerging class of contaminants, scientists studied what fate befalls these organisms in the sewage treatment plants.
And to this end, the researchers collected samples of raw influent and treated effluents from twelve sewage treatment plants across Delhi. They tested these samples for microbial density and presence of drug-resistant genes.
Because beta-lactams are the most widely prescribed drugs in the country, the scientists decided to focus on this class of drugs. Penicillin, the first antibiotic to be discovered, also falls in this class but, gradually, due to unrestricted consumption, most members of this group have become ineffective against common infections.
Most bacteria tackle drugs by altering their genetic code. The small changes that bacteria engender in their genes help them produce proteins that can destroy the drug. That is why many drugs fail, explains Manisha Lamba, a researcher in Ahammad’s lab and the lead author of this study. Resistance to beta-lactams is developed when microbes begin producing a protein called beta-lactamase that can digest these drugs.
The scientists were interested in gauging resistance to two members of beta-lactams: extended spectrum beta-lactams (ESBL) and carbapenems. They grew microbes from sewage samples in the presence of these drugs. All those microbes that were resilient to ESBL and carbapenem could thus be isolated. Next, they extracted the bacterial DNA from sewage samples and looked for genes that code beta-lactamases specific for ESBL and carbapenem.
During the course of the study, scientists found that many sewage treatment plants are not equipped for the advanced treatment of wastes. Out of the 12 studied plants, only two had the technology for chemical treatment while the remaining 10 discharged their effluents without chemical disinfection. Effluents that were not treated with chemicals or subjected to any other form of tertiary treatment carried similar amounts of drug-resistant bacteria as the raw sewage.
“These results are not particularly surprising,” says Ahammad. “When treatment plants were first conceived their main aim was to tackle organic pollutants in the sewage, not target microbes.”
But there’s another thing that raises concern: In almost all treatment plants, the amount of drug-resistant bacteria was related to the load of faeces in the sewage. Scientists posit that this is because of faeces being contaminated with antibiotics. Most drugs that we consume are not broken down in the body and are released with the faeces. When human and animal excreta rich in these compounds are bundled together in the treatment chambers it creates an environment conducive for the development of drug resistance. The presence of organic matter in the slew also promotes the growth of bacteria. What’s more alarming is that even when the bacterial load was reduced, there was no significant change in the frequency of antibiotic-resistant genes extracted from the treated effluent.
“This means that the bacteria which were resistant to only one family of drugs prior to sewage treatment acquire multidrug resistance by the end of the process,” Ahammad told The Wire.
“This slew rich in drug-resistant bacteria is dumped in the Yamuna. Just imagine the health risks this can create.”Over the past few years, Delhi has seen a surge in the number of drug-resistant infections. “We have witnessed the development of ESBL-producing gram-negative bacteria, NDM-1-producing enterobacteriaceae, multidrug-resistant enterococci, multidrug- and extensively drug-resistant mycobacteria and methicillin-resistant Staphylococcus aureus,” says Rama Chaudhry, an ambassador from the American Society for Microbiology to India. “It is a grave situation as we are left with few antibiotics to treat many hospital-acquired infections.”
Resistance against carbapenem
From the treated effluents, scientists could isolate a wide range of drug-resistant bacteria that cause a plethora of common infections. Most prominent among them were Escherichia coli that causes dysentery and Klebsiella pneumoniae that causes pneumonia. Both these strains were found to be resistant to ESBL and carbapenems. Resistance against carbapenem is a cause for worry because they are the last line of defence against many multidrug-resistant bacteria. For a very long time carbapenem was a panacea for multidrug-resistant infections. But now that the bacteria have learnt to overcome this drug, the options for treating drug-resistant infections is becoming very limited.
This is also of concern because the genetic fragments that code for drug resistance can be exchanged between bacteria. The ease with which this happens depends on the frequency of repetition of DNA fragments called integrons. They serve as a capture and transport system for antibiotic resistance genes. And together with the gene, they also move the components necessary for its successful installation and propagation in the other bacterium.
Both ESBL- and carbapenem-resistant genes matched the frequency of integrons simply denoted 1 and 3 in the treated sewage samples. Integrons 1 and 3 are active propagators of genetic transfer. So the presence of drug-resistant bacteria in the released effluents can also accelerate the spread of antibiotic resistance in the environment, cautions Ahammad.In 2014, the World Health Organisation identified the high risk of antibiotic resistant diseases in our country. As the death toll from drug-resistant infections continues to rise, this has become a particularly pertinent issue for India.
Based on their findings, the researchers have proposed a treatment scheme to lower the load of drug-resistant bacteria in the sewage.
Their research shows that chemical disinfection could reduce the load of ESBL and carbapenem-resistant bacteria in the effluents by 100 folds. The incorporation of anaerobic sludge digester could further reduce the microbial density in treated sewage.
“The study clearly reiterates that it is very important to have our sewage treatments plants working efficiently and at full capacity in our endeavours, among many other measures, to fight the menace of antimicrobial resistance in our country,” says Jugsharan Singh Virdi, a scientist at the department of microbiology, University of Delhi. “Just by adding another treatment step in processing the sludge and the slurry could sufficiently reduce the amount of antibiotic-resistant bacteria in the discharge,” says Lamba. This should suffice for now.
Next, the scientists plan to map the levels of drug-resistant bacteria in sewage collected from different areas of Delhi. This would help policymakers take action on a case by case basis. “These changes would cost money but that would be insignificant compared to the economic burden we bear due to communicable diseases,” says Ahammad.
Sarah Iqbal is a senior research fellow at the department of biochemistry, Aligarh Muslim University, India.