The article by Laura J. V. Piddock provides an in-depth review of chromosomally encoded multidrug resistance (MDR) efflux pumps in bacteria. Efflux pumps are proteins that pump antimicrobial agents out of the cell, and their overexpression can lead to resistance to various antibiotics and other antimicrobial agents. The review covers the structure, function, and clinical relevance of these pumps, focusing on five major families: resistance nodulation division (RND), major facilitator superfamily (MFS), staphylococcal multiresistance (SMR), multidrug and toxic compound extrusion (MATE), and ATP binding cassette (ABC) transporters. Key points include: - **Genomic Distribution**: Efflux pump genes can be found on the chromosome or on mobile elements like plasmids. - **Structural Organization**: RND pumps are organized as tripartite systems, involving a transporter protein, a periplasmic accessory protein, and an outer membrane channel. - **Substrates**: These pumps can transport a range of structurally diverse compounds, including antibiotics, disinfectants, dyes, and detergents. - **Clinical Relevance**: Overexpression of efflux pumps can lead to MDR in bacteria, affecting the effectiveness of antimicrobial treatments. This is particularly relevant for gram-negative bacteria like *Pseudomonas aeruginosa* and *Escherichia coli*, as well as food-borne pathogens like *Salmonella enterica* and *Campylobacter jejuni*. - **Regulation**: Mutations in local repressor genes, global regulatory genes, promoter regions, and insertion elements can increase efflux pump expression, leading to resistance. - **Inhibitors**: Several inhibitors have been identified that can block efflux pump activity, providing potential targets for developing new antibiotics. The article highlights the importance of understanding these efflux pumps in the context of antimicrobial resistance and the need for continued research to develop effective strategies to combat MDR bacteria.The article by Laura J. V. Piddock provides an in-depth review of chromosomally encoded multidrug resistance (MDR) efflux pumps in bacteria. Efflux pumps are proteins that pump antimicrobial agents out of the cell, and their overexpression can lead to resistance to various antibiotics and other antimicrobial agents. The review covers the structure, function, and clinical relevance of these pumps, focusing on five major families: resistance nodulation division (RND), major facilitator superfamily (MFS), staphylococcal multiresistance (SMR), multidrug and toxic compound extrusion (MATE), and ATP binding cassette (ABC) transporters. Key points include: - **Genomic Distribution**: Efflux pump genes can be found on the chromosome or on mobile elements like plasmids. - **Structural Organization**: RND pumps are organized as tripartite systems, involving a transporter protein, a periplasmic accessory protein, and an outer membrane channel. - **Substrates**: These pumps can transport a range of structurally diverse compounds, including antibiotics, disinfectants, dyes, and detergents. - **Clinical Relevance**: Overexpression of efflux pumps can lead to MDR in bacteria, affecting the effectiveness of antimicrobial treatments. This is particularly relevant for gram-negative bacteria like *Pseudomonas aeruginosa* and *Escherichia coli*, as well as food-borne pathogens like *Salmonella enterica* and *Campylobacter jejuni*. - **Regulation**: Mutations in local repressor genes, global regulatory genes, promoter regions, and insertion elements can increase efflux pump expression, leading to resistance. - **Inhibitors**: Several inhibitors have been identified that can block efflux pump activity, providing potential targets for developing new antibiotics. The article highlights the importance of understanding these efflux pumps in the context of antimicrobial resistance and the need for continued research to develop effective strategies to combat MDR bacteria.