Destroying Bacterial Cell Walls May End Antibiotic Resistance Forever
Bacteria is starting to become drug resistant and this is very dangerous, this is happening on a big scale because the bacteria are able to develop an extra wall. An thats’s the simple reason how bacteria is becoming immune to antibiotics, a lipid-based outer membrane in “gram-negative” bacteria prevents infiltration by conventional antibiotic drugs and natural immune system responses. There hasn’t been any countermeasures leading to the bacteria turning fully virulent and running wild with the consequences of possibly causing death. So penetrating or toppling this wall has been one of a key fronts in the microbial arms race.
The wall can be found in gram-negative bacteria and is actually a second membrane, composed of large molecules called lipopolysaccharides or LPS. LPS is both an endotoxin and pyrotoxin, which is bad for a range of reasons. It can cause spiking fevers which turn’s up the bodies natural thermostat as well as generally being a handful for the immune system. As LPS molecules reach a critical mass within the human body, in fact the human body is more vulnerable to this kind of attack than other animals, this will cause septic shock results and death will not be that far away.
Note that all of the above is in addition to the LPS wall’s role in keeping our defenses, natural and otherwise, at bay. Typically, diffusion of molecules across this membrane and into the bacterial guts, where said bacterium can be destroyed or rendered harmless, is mediated by tiny channels called porins. It’s these porins that adapt in size to keep antibiotics or other threats on the outside. Gaining access through these ports has been a long-standing challenge in antibiotic development, but a study out this week in the journal Nature describes the “Achilles’ heel” of this bacterial defensive strategy, a mechanism for not just killing bacteria off, but preventing the development of resistance in the first place.
The success will eventually come but not from crashing the gram-negative gateway or hero molecules designed to tear down and penetrate the membrane as well. Instead preventing of this membrane/wall being developed or reinforced in the first place. The outer wall gains reinforcement from the inner wall via a path, so if you sabotage the path then the outer wall will be very easy to penetrate and be very weak.
“We have identified the path and gate used by the bacteria to transport the barrier building blocks to the outer surface,” said research team leader Changjiang Dong in a statement. “Importantly, we have demonstrated that the bacteria would die if the gate is locked.”
More specifically, the researchers were able to finely map the the “barrel-like” structures that move LPS materials to the outer membrane, for the very first time.
“Seven LPS transport proteins form a trans-envelope protein complex responsible for the transport of LPS from the inner membrane to the outer membrane, the mechanism for which is poorly understood,” the study reports. “LptE [one of the transport proteins] adopts a roll-like structure located inside the barrel of LptD to form an unprecedented two-protein ‘barrel and plug’ architecture,” that allows membrane building materials out, but prevents drugs or damaging immune system agents from getting it.
With this method a big advantage is that it will only attack this second wall and not the actual bacterium. According to the study’s lead author Haohao Dong, this fact might lead to the treatment to finally end all treatments. “Because new drugs will not need to enter the bacteria itself,” he said, “we hope that the bacteria will not be able to develop drug resistance in future.”
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