United States: A deadly pathogen that looks like a handful of pebbles stacked together under a microscope had been a nightmare for the scientific community until recently.
The pathogen or superbug called carbapenem-resistant Acinetobacter baumannii, or CRAB, has the potency to kill roughly half of all patients who acquire it.
Researchers recently, after doing the research for half a century, finally have identified a new antibiotic that appears to effectively kill A. baumannii, Los Angeles Times reported.
Why is CRAB called a superbug?
Carbapenem-resistant A. baumannii is a type of gram-negative bacteria that is hard to deal with, a group called superbugs.
It is the most common form of a group of bacteria that are resistant to nearly all available antibiotics. Protected by an inside and outside layer that medicine has trouble getting through, gram-negative bacteria are hard to treat with usual therapies.
They are unusually smart unicellular organisms that possess the ability to rapidly develop new defenses against antibiotics and then pass them along to other bacteria through genetic material.
It was identified as a top-priority pathogen by both the World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC), the Los Angeles Times reported.
High Death count by the superbug
The infected patients are generally hospitalized who are already sick with blood infections or pneumonia.
In the US alone, the bug sickens thousands and kills hundreds every year. Globally, Antibiotic-resistant superbugs claim the lives of over 1 million people annually, Los Angeles Times reported.
The increase in drug resistance is partly because of human mistakes, i.e., humans have long over-prescribed and misused antibiotics.
However, it also happens because the bacteria continually find ways to avoid the danger all the time. In the last 50 years, these pathogens have changed their defenses quicker than the experts make new drugs.
About newly developed antibiotic drug
The drug was jointly developed by the scientists at The Swiss pharmaceutical company Roche and Harvard University. The findings were published in the journal Nature on Wednesday.
The Roche and Harvard scientists, looking for a new weapon, turned their attention to a group of compounds called tethered macrocyclic peptides (MPs). After testing a library of 45,000 MPs, the researchers came across one that seemed especially deadly against A. baumannii. After some chemical alterations, that compound became zosurabalpin.
The compound zosurabalpin attacks bacteria from a novel angle. It disrupts the path for a key toxin produced inside the bacterial cells from inside of the cell to the outer membrane. It shields the bug from the immune system’s defensive onslaughts.
As per the report from the Los Angeles Times, no other antibiotic approved by the US Food and Drug Administration takes this approach.
Paul J. Hergenrother, a chemistry professor at the University of Illinois who was not involved in the research but wrote of the findings for Nature, said, “This is a very promising advance,” and added further, “Zosurabalpin kills bacteria in a way that is different from all other approved antibiotics,” according to Los Angeles Times.
This antibiotic has proved to be effective against even the smallest of the enemies.
A. baumannii has had no opportunity to develop resistance against the drug, which means that, for at least a little while, zosurabalpin could ward off severe illness and death.
The drug acts only in the presence of lipopolysaccharide (LPS), a bacterial toxin. LPS is made inside the bacterial cell and is carried by a dedicated transport system to the bug’s outer defenses.
Zosurabalpin mainly stops the way LPS travels without a way to get to the outer membrane of the cell, where it can start working against drugs and immune attacks. The toxins rise inside the bacteria, which eventually kills them.
Kenneth Bradley, Roche’s global chief of discovery for infectious diseases, said, “The bacterial outer membrane is important for bacteria because it helps them live in harsh conditions and survive attacks by our immune system.”
Dr Oladele A. Ogunseitan, a professor of population health and disease prevention at UC Irvine who was not involved with the study, said, “As far as I can tell, the scientific approach is brilliant.”
Findings from the trials
During studies tested on mice, the drug effectively killed off CRAB infections in the blood, lungs, and thighs, a selection that reflects the ways the bug infects humans.
In human testing, it’s on Phase 1 trials where researchers are majorly focusing on the drug’s safety, tolerability, and the amount of the chemical that remains in patients’ bodies over time, said Michael Lobritz, Roche’s infectious diseases chief, Los Angeles Times report.
Lobritz also mentioned, “It has been more than 50 years since the last distinct class of antibiotic was launched that is capable of treating infections by Gram-negative bacteria,” and “Any new antibiotic class that has the ability to treat infections caused by multidrug-resistant (MDR) bacteria such as carbapenem-resistant Acinetobacter baumannii (CRAB) would be a significant breakthrough.”
The scientists are stressing that it would be foolish to consider that the fight against the bug is over since, time and time again, it has found ways to evade most advanced pharmaceutical weaponry.
Bradley said, “Resistance has emerged to every antibiotic ever created, and it is likely that resistance will emerge to zosurabalpin in the future, too, if it successfully becomes a clinical antibiotic.”
According to Ogunseitan, “Although the rates of appearance of these resistant organisms are low and comparable to standard-of-care antibiotics, the observation affirms the principle that we can never rest on our laurels with the chemical and biochemical warfare that we are waging on bacterial pathogens.”