New Strain Of Extensively Drug Resistant (XDR) Samonella Bacteria Emerges And Is Evolving As A Deadly Killer

Thailand Infectious Diseases

The first extensively drug-resistant (XDR) strain of Salmonella typhimurium, called ST313 sublineage II.1, has evolved in the African Continent and is slowly spreading towards other worldwide locations. This new form of bacterial infection fails to respond to any of the antibiotics that are commonly used except for ciprofloxacin. But what is alarming is that new mutated strain samples have been isolated, showing incomplete response even to this last drug.  
The bacterium S. typhimurium, which many researchers say originated in sub-Saharan Africa some decades ago, has been showing increasingly broad resistance to antibiotics over the last decades.
 
According to the new study which reports the emergence of this new strain of S. typhimurium in the journal Nature Communication, this is a threat which will need the close cooperation of microbiologists, geneticists, and epidemiologists, in addition to clinicians and other specialists, if it is to be identified and controlled in different locations.
 
Typically Salmonella is more commonly known to cause food poisoning, not necessarily life-threatening.
 
However, the new strain S. typhimurium and related strains, which are better known to cause bloodstream infections, can be fatal. In fact, these have gained their own name: invasive non-typhoidal Salmonella (iNTS) infections. Such infections affect almost 3.5 million people a year, and almost 700,000 thousand individuals die from it, with the greatest danger coming from S. typhimurium.
 
These iNTS infections are rife in the very places which have the lowest availability of healthcare, a poorly equipped system, and low levels of immunity. In these places, it is the children under 5 years of age who bear the brunt.
 
The exact strain of S. typhimurium producing iNTS in this region is typically ST313, which is known to be resistant to drugs. This has also given rise to two new variants called lineage I and lineage II, which have spread independently to cover most of Africa, fueled by two factors: HIV prevalence and multidrug resistance (MDR). Lineage II infections are now the main cause of iNTS.

Extensively "> Drug Resistant (XDR) Infectious Bacteria

 
MDR pathogens are resistant to ampicillin, trimethoprim/sulfamethoxazole and chloramphenicol. This should not create a problem with iNTS, which is typically treated with the fluoroquinolone antibiotic ciprofloxacin. On the other hand, complicated iNTS requires ceftriaxone, but ST313 lineage II is now showing the presence of extended-spectrum beta-lactamase enzymes, which means they do not respond to newer cephalosporins either, like ceftriaxone. This fits the definition of XDR as applied to S. typhi, that is, resistant to five drugs.
 
Expanded, this means the bacteria show MDR along with resistance to the two second-line drugs, ceftriaxone (through extended-spectrum beta-lactamase enzymes), and azithromycin. This leaves only the fluoroquinolones. However, one sample has already been isolated which is not susceptible to this either – a pan-resistant pathogen. This evolving strain, dubbed lineage II.1, is responsible for more than 10% of isolates in the central part of Africa and has been found in countries like China and Cambodia and Myanmar.
 
The most worrying part is yet to come. Not only is the bacterium becoming increasingly resistant to all antibiotics, but it is evolving towards becoming a primary bloodstream pathogen. In the first case, researchers found that a single plasmid carried all the resistance genes. A plasmid is a package of genetic material that can be transferred from cell to cell. Moreover, the new lineage II strain is undergoing several changes, both in its genome and in its behavior, which means it is becoming more and more geared up for bloodstream infections, becoming “invasive”, in other words.
 
Invasive characteristics have been detected both in laboratory experiments as well as by the innovative use of machine learning algorithms. These techniques helped to pick up characteristic patterns in the DNA that indicate which strains are becoming invasive. These include less stimulation of the host immune system, lower metabolism, loss of one type of flagella and greater tendency to form biofilms.
 
Excessive and misuse of antibiotics are possible reasons for this occurrence, says the study. Azithromycin was recently used in a mass campaign to wipe out trachoma, an infectious cause of blindness, and also is extensively used in children. The plasmid found in lineage II strains has previously been found in other iNTS-associated S. typhimurium.
 
Over the last 8 years, all bloodstream infections have been put under surveillance by two agencies, the DRC’s Institut National de Recherche Biomédicale (INRB) and the Institute of Tropical Medicine (ITM) in Antwerp. The routine isolation of the causative organisms from patients across the country has proved a great help in picking up the earliest indications of bloodstream infections with this XDR strain of S. typhimurium. With hundreds of blood samples collected from patients in Africa who were suspected to have sepsis, the emergence of drug resistance to S. typhimurium on an order never before imagined is becoming clear. Scientists have put in place a worldwide effort to trace the continuing development of ST313, and to assess its resistance to antibiotics.
 
The evolving S. typhimurium. Strain could be the next major fatal epidemic of the 21^st century if measures are not undertaken to control its spread and also to find a treatment protocol. Already the fact that its evolved strains are finding its way into other locations out of Africa is already an indication of a major healthcare disaster waiting to happen. The CDC and WHO has yet to acknowledge the seriousness of this new bacterial strain and its spread, its evolution into a bloodstream pathogen and further mutations that its undergoing.
 

Reference:

An African Salmonella typhimurium ST313 sublineage with extensive drug-resistance and signatures of host adaptation. Sandra Van Puyvelde, Derek Pickard, Koen Vandelannoote, Eva Heinz, Barbara Barbé, Tessa de Block, Simon Clare, Eve L. Coomber, Katherine Harcourt, Sushmita Sridhar, Emily A. Lees, Nicole E. Wheeler, Elizabeth J. Klemm, Laura Kuijpers, Lisette Mbuyi Kalonji, Marie-France Phoba, Dadi Falay, Dauly Ngbonda, Octavie Lunguya, Jan Jacobs, Gordon Dougan & Stijn Deborggraeve. Nature Communications, volume 10, Article number: 4280 (2019). https://doi.org/10.1038/s41467-019-11844-z. https://www.nature.com/articles/s41467-019-11844-z