Soil harbors a vast reservoir of antimicrobial agents. In fact, approximately 80% of all clinically implemented antibiotics are derived from soil-dwelling bacteria. However, many bacteria have evolved methods to evade the effects of various antibiotics and thus have acquired resistance to these chemical substances. Today, the increasing resistance of many common disease-causing bacteria to antibiotics is a global health crisis. Therefore, scientists are seeking to develop new antibiotics that can overcome the resistance capabilities of numerous pathogenic bacteria. Arylomycins are considered to be among the most promising of these new compounds. See also: Antibiotic; Antibiotic resistance; Antibiotic resistance in soil bacteria; Antimicrobial agents; Bacteria; Infectious disease; Medical bacteriology; Microbiology; Pathogen; Public health; Soil; Soil microbiology

Two rod-shaped Klebsiella pneumoniae bacteria (digitally colorized gold) interact with human white blood cells (digitally colorized gray). Klebsiella pneumoniae bacteria have developed resistance to a variety of antibiotics. However, newly synthesized derivatives of arylomycins are being tested as antibiotics because various Gram-negative pathogenic bacteria, such as K. pneumoniae, do not display any resistance to these compounds. (Credit: National Institute of Allergy and Infectious Diseases)

Arylomycins are macrocyclic lipopeptides that are found commonly in soil. Previously, researchers noted that these compounds inhibit a cell-membrane enzyme called type I signal peptidase (SPase), which is necessary for the secretion of key functional proteins in bacteria. By blocking the SPase enzyme, the bacterial proteins are retained in the cell membrane, leading to membrane bursting and, ultimately, death of the cell. (In contrast, most other antibiotics work by either weakening the walls of cells or disabling the production of various proteins.) In particular, the arylomycins worked most effectively against Gram-negative bacteria, including Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli (note that Gram-negative bacteria do not retain the crystal violet dye in the Gram staining method and thus appear pink or red in color). However, the natural arylomycin forms often had difficulty in binding to potential bacterial targets, limiting their efficacy and the spectrum of their activity. Therefore, investigators modified the natural compounds synthetically, broadening the spectrum of activity of these derivatives and enabling them to become more effectual at binding their targets. As a result of these modifications, the arylomycins became more potent at killing Gram-negative bacteria. See also: Enzyme; Escherichia; Klebsiella; Macrocyclic compound; Pseudomonas; Stain (microbiology)

The results of studies using arylomycins have been promising in both laboratory-dish tests and multiple mouse models. Most important, the arylomycin antibiotics retained full operational capabilities against 49 multidrug-resistant Gram-negative strains. Moreover, the modified arylomycins displayed few or no side effects, thereby encouraging researchers to continue further development of these compounds. If successful in human trials, the arylomycins might become the first new antibiotic group to be approved by federal agencies in decades, adding a new strategic tool in the fight against antibiotic resistance. See also: Clinical microbiology; Drug resistance