Bengal Bay Clone: The Origin of the Superbug Ravaging Hospitals

Bengal Bay Clone: The Origin of the Superbug Ravaging Hospitals

Over the last decade, a multi-drug resistant bacterial pathogen, known as the Bay of Bengal clone, has emerged in community and hospital environments in Asia, Australasia, Africa, the Middle East, and Europe.

The Bengal Bay clone (ST772) is a multidrug-resistant, methicillin-resistant Staphylococcus aureus (MRSA) strain. It was first described in the 1990s with reports of it causing severe disease in India. It was first isolated from Bangladesh and India in 2004.

MRSA is principally a threat to hospital patients and those with compromised immune systems, often leading to life-threatening conditions such as sepsis. MRSA is considered an important contributor to the difficult-to-treat bone and joint infections in India. More recently, MRSA clones, including the Bay of Bengal counterpart, have been causing major problems in the community setting in patients who have never been to the hospital.

Using whole-genome sequencing, researchers have now traced the Bay of Bengal clone’s likely birthplace to the Indian subcontinent and mapped its subsequent intercontinental transmission.

Steven Tong, associate professor at the Peter Doherty Institute for Infection and Immunity in Australia, and his team found the Bengal Bay clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly through the 1990s and early 2000s.

Steven Tong, Associate Prof, Peter Doherty Institute“We noticed this clone was appearing around the world and wanted to study it further. It seems to be able to cause extensive disease, although not necessarily more deadly than other clones.”

The researchers generated whole-genome sequence data of 340 samples of the Bay of Bengal clone from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage.

Published in the journal mBio, researchers were able to show step-by-step mutations of the Bengal Bay clone, narrowing down the timeline of increasing resistance to different antibiotics and when it was exported across international borders.

“By being able to map the Bengal Bay clone over many years, we were able to see it progressively acquire specific antibiotic resistance mechanisms, following which it achieved global transmission through family contacts or travel. Several small-scale community and health care outbreaks were evident after importation to countries outside the Indian subcontinent.”

Antibiotic Resistance and Rise of Superbugs

The main drivers behind the emergence and spread of the Bay of Bengal clone are the acquisition of resistance to antibiotics.

Tong said the main drivers behind the emergence and spread of the Bay of Bengal clone are the acquisition of resistance to antibiotics, contribution of travel and also social determinants of health in the Indian subcontinent.

“We found that international travel and family connections to the region (India, Bangladesh, Nepal, and Pakistan) were closely linked with the global spread of the lineage,” the authors write in the study, pointing to extrachromosomal DNA called plasmids in being “instrumental” in the emergence of a single dominant and globally disseminated clade (group) in the early 1990s.”

(Plasmids are extra pieces of genetic material found in many cells that usually confer a specific property to the cell.)

The researchers underscore that the Bengal Bay clone combines a high level of both antibiotic resistance (a feature of traditional healthcare-associated MRSA) and virulence (characteristic of community-associated MRSA).

“MRSA has typically been associated with hospitals and patients in the hospital. These hospital clones are often resistant to multiple antibiotics. But these clones usually cause infections in vulnerable patients. The community clones are usually resistant to only methicillin (or 1-2 other antibiotics) – they are not multi-resistant. But they do cause infections in otherwise healthy hosts (not just vulnerable hosts)."

"So this Bengal Bay clone is both multi-resistant and is able to cause infections in otherwise healthy hosts,” explained Tong.

Considering the widespread use of antibiotics and associated poor antibiotic regulation, limited public health infrastructure, and high population density in parts of South Asia, the emergence and global dissemination of multidrug-resistant bacterial clones are alarming and perhaps not surprising, the study said.

The authors highlight the urgent need for antimicrobial stewardship at the community, health care, and agricultural levels.

Tong said some degree of systematic surveillance of clinical disease due to Staphylococcus aureus together with data on these cases of antibiotic resistance patterns and ideally genome sequencing of a selection of these isolates to understand the epidemiology could be potential monitoring and surveillance solutions for India and South Asia.

According to a UN Ad hoc Interagency Coordinating Group on Antimicrobial Resistance report, drug-resistant diseases could cause 10 million deaths each year by 2050 and damage to the economy as catastrophic as the 2008-2009 global financial crisis. By 2030, antimicrobial resistance could force up to 24 million people into extreme poverty.

Currently, at least 700,000 people die each year due to drug-resistant diseases, the report said.

India and Antibiotic Resistance

India, one of the largest consumers of antibiotics in the world, also shows high levels of resistance to most commonly consumed antibiotics in the country, according to a 2019 study that listed India, Thailand, Ecuador and Venezuela, as the low and middle-income countries (LMICs) that had the highest Drug Resistance Index (DRI), a measure that allows for global assessment of the relative efficacy of countries’ antibiotic therapy.

Resistance rates for the priority pathogens, including Staphylococcus aureus, remain at a level that threatens public health, and the relative effectiveness of antibiotic therapy in LMICs is lower than in high-income countries. The DRI scores demonstrate that not only do these countries suffer from a high burden of disease, but they also reflect a relatively lower level of antibiotic effectiveness due to less access to newer, more effective antibiotics.

Resistance rates for the priority pathogens, including Staphylococcus aureus, remain at a level that threatens public health, and the relative effectiveness of antibiotic therapy in LMICs is lower than in high-income countries. The DRI scores demonstrate that not only do these countries suffer from a high burden of disease, but they also reflect a relatively lower level of antibiotic effectiveness due to less access to newer, more effective antibiotics.

Terming the study significant, microbiologist Yogesh Shouche, Principal Investigator of National Centre for Microbial Resource (NCMR) at the National Centre for Cell Science, Pune, said there is an increasing awareness on the emergence and cross-border spread of superbugs in India.

“Among the superbugs thought to have originated in India and gone abroad, the NDM gene is the most well known. There will be many bugs that have evolved somewhere else and have come to India,” said Shouche, adding colistin resistance might have emerged in Europe because the first case of colistin resistance in Klebsiella pneumoniae in 2004 was reported in Athens and in Acinetobacter baumanii in Czech Republic in 1999.

Considering antimicrobial resistance (AMR) as a national priority, under National Action Plan endorsed by the Indian government, the Department of Biotechnology has initiated a major mission program on antimicrobial resistance.

The program aims to develop indigenous and cost-effective therapies against AMR; categorisation of AMR-specific pathogen priority list of India; establishment of bio-repository (biobank) for AMR-specific pathogens; and development of rapid and cost-effective diagnostic kits to identify AMR-specific pathogens.

The biobank at NCMR, Pune has started receiving isolates from partner hospitals, said Shouche.

“Presently we have 16 MRSA isolates The repository will have well characterised AMR strains as reference material that can be used to study the spread of AMR, development of new drugs and developing diagnostic tools,” Shouche told FIT.

(Sahana Ghosh is a microbiologist-turned-journalist. She writes on science and environment and is interested in science in remote areas.)