#Gram negative bacteria membrane skin#

We performed a genetic screen to identify genes important for the OM barrier of A.

#Gram negative bacteria membrane skin#

Similar to other Gram-negative opportunistic pathogens such as Pseudomonas aeruginosa and Klebsiella spp., individuals with breached skin or damaged respiratory tract mucosa are most vulnerable ( Chmelnitsky et al., 2013 Abbo et al., 2005).

Although progress has been made in understanding many aspects of OM assembly – including the discovery of an LPS transport system and the machinery for proper folding and insertion of outer membrane proteins ( Okuda and Tokuda, 2011 Okuda et al., 2016) – little is known about the molecular mechanisms for transport of the GPLs necessary for OM formation and barrier function.Īcinetobacter baumannii is an important cause of antibiotic-resistant opportunistic infections and has significant innate resistance to disinfectants and antibiotics. The asymmetric nature of its lipid bilayer and the structure of LPS/LOS molecules facilitates barrier function, as the core region of LPS impedes the entry of hydrophobic molecules into the cell while the acyl chains within the bilayer also help to prevent the entry of many hydrophilic compounds ( Bishop, 2014). The OM forms the first line of defense against antimicrobials by functioning as a molecular permeability barrier. In contrast, the outer membrane (OM) is largely asymmetric and composed of an inner leaflet of GPL and an outer leaflet of lipopolysaccharide (LPS) or lipooligosaccharide (LOS) ( Pelletier et al., 2013). The inner membrane (IM) is a symmetric bilayer of glycerophospholipids (GPL), of which zwitterionic phosphatidylethanalomine (PE), acidic phosphatidylglycerol (PG), and cardiolipin (CL) are among the most widely distributed in bacteria ( Zhang and Rock, 2008). Gram-negative bacteria are enveloped by two lipid bilayers, separated by an aqueous periplasmic space containing a peptidoglycan cell wall. By learning more about the outer membrane, we may be able to create new treatments to bypass or to disable this shield, for example by targeting the Mla system. The experiments also showed that a working Mla system was required for bacteria to survive antibiotics.Ĭertain dangerous Gram-negative bacteria are now resistant to many drugs, having evolved unique envelopes that keep antibiotics at bay. Amongst them, four genes coded for a transport machine, the Mla system, which allowed GPLs to cross the inner membrane and reach the outer membrane. Sequencing these blue bacteria revealed 58 genes involved in keeping the outer membrane working properly. If colonies became blue, this meant that the mutations had happened in a gene essential for the outer membrane. then introduced genetic changes at random locations in the genomes of the bacteria. If the outer membrane is not working properly, the compound can cross it and the cell turns blue. exposed a species of Gram-negative bacteria to a molecule that is normally blocked by the outer membrane. To investigate these questions, Kamischke et al. For example, it was still unclear how GPLs were exported through the inner membrane to the outer one. Very little is known about how this external shield is created and maintained. It is made of a complex assembly of molecules, including glycerolphospholipids (GPL) that are produced inside the cells. The outer membrane lets nutrients penetrate inside the cell, but blocks out other compounds, such as antibiotics. This casing is formed of an inner and an outer membrane, which have different structures and properties. Gram-negative bacteria are a large group of single-celled organisms that share a typical external envelope. The importance of the Mla system to Acinetobacter baumannii OM integrity and antibiotic sensitivity suggests that its components may serve as new antimicrobial therapeutic targets. The broad conservation of the Mla system in Gram-negative bacteria suggests the system may play a conserved role in OM biogenesis. We further show that this opportunistic, antibiotic-resistant pathogen uses this multicomponent protein complex and ATP hydrolysis at the inner membrane to promote GPL export to the OM. We screened Acinetobacter baumannii transposon mutants and identified a number of mutants with OM defects, including an ABC transporter system homologous to the Mla system in E. The OM is asymmetric and contains an outer leaflet of lipopolysaccharides (LPS) or lipooligosaccharides (LOS) and an inner leaflet of glycerophospholipids (GPL). The outer membrane (OM) of Gram-negative bacteria serves as a selective permeability barrier that allows entry of essential nutrients while excluding toxic compounds, including antibiotics.