A team led by Daniel López, a CSIC scientists in the Centro Nacional de Biotecnología, has developed a strategy to deactivate a mechanism that gives bacteria antibiotic resistance.
It is based on the use of molecules, designed by the scientific team, which target specifically the microdomains of the bacterial membrane where proteins are assembled to form protein complexes. This microdomains, called ‘lipid rafts’, play an essential role because “many protein complexes related to antibiotic resistance are formed there”, López explains.
The designed molecules break the microdomains and provoke the disruption and disorganization of bacterial proteins, which makes impossible the antibiotic resistance.
The new molecules have been tested on rodents infected with Staphylococcus aureus, a common bacteria and main cause of hospital infections. The most common strains of this bacteria are methicillin-resistant. A treatment of methicillin combined with the new molecules could be a strategy to overcome the problem of resistance.
The results of the work, which have been published in the Cell journal, demonstrate the strategy is effective. To keep on with the research, the scientific team is considering to test the strategy in a hospital environment. “Because these are a very controlled environment”, says Daniel López, “we could do an essay having baseline data, a procedure record and patients to start the research. Also, hospitals are environments where antibiotic resistance is specially harming”.
Would the strategy be effective for many bacterial infections? As Lopez answers, more tests are necessary to know it.
The bacterial lipid rafts
“Confination of cellular processes to make them more efficient is something that usually happens in nature; we have seen it in eukaryotic cells, which have their DNA processes confinated in the nucleus, their breathing processes confinated in the mitochondria…”, explains Daniel López.
The discovery that bacteria, which are apparently simply organisms, do also organize its processes in closed compartments is a relevant result of the work. In this case, as the scientists explain, we hypothesize that bacterial lipid rafts are platforms that confine protein oligomerization.
CSIC scientists at the lab in the CNMB-CSIC. Daniel Lopez, at the right. Picture: Lucas Melcón-Comunicación CSIC.“I often give this example to the young scientists in my lab”, says Daniel López. “Imagine you go to New York to meet the woman of your life, whose name you know but not the address or her physical aspect… the chances you will meet her in such a big space are small. But imagine you are in a confined space, a party for example, where both of you are invited: now chances that you interact with her are higher. And imagine there is a friend of yours at that party, who also knows her: now interaction will very probably happen. This is exactly what happens in the lipid rafts: there is a chaperone protein, called Flotillin, which facilitates the interaction of proteins that oligomerize”.
The developed strategy would only be effective for bacteria that produce the lipids that can form these lipid rafts.
Although this strategy would not work for all bacterial species, scientists think it could be useful to fight some resistant bacteria, such as Streptococcus pneumoniae, Legionella pneumophila or Listeria monocytogenes. “We are optimistic about the potential of this treatment, we think there are many possibilities to explore”, says López.
Video: https://youtu.be/TgLmpz44VFk
Reference article:
Esther García-Fernández, Gudrun Koch, Rabea M. Wagner, Agnes Fekete, Stephanie T. Stengel, Johannes Schneider, Benjamin Mielich-Suss, Sebastian Geibel, Sebastian M. Markert, Christian Stigloher y Daniel López. Membrane Microdomain Disassembly Inhibits MRSA Antibiotic Resistance. Cell. DOI: 10.1016/j.cell.2017.10.012