Gram-negative bacteria

Gram-negative bacteria are bacteria that, unlike Gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists of a thin peptidoglycan cell wall sandwiched between an inner (cytoplasmic) membrane and an outer membrane. These bacteria are found in all environments that support life on Earth.

Within this category, notable species include the model organism Escherichia coli, along with various pathogenic bacteria, such as Pseudomonas aeruginosa, Chlamydia trachomatis, and Yersinia pestis. They pose significant challenges in the medical field due to their outer membrane, which acts as a protective barrier against numerous antibiotics (including penicillin), detergents that would normally damage the inner cell membrane, and the antimicrobial enzyme lysozyme produced by animals as part of their innate immune system. Furthermore, the outer leaflet of this membrane contains a complex lipopolysaccharide (LPS) whose lipid A component can trigger a toxic reaction when the bacteria are lysed by immune cells. This reaction may lead to septic shock, resulting in low blood pressure, respiratory failure, reduced oxygen delivery, and lactic acidosis.

Several classes of antibiotics have been developed to target Gram-negative bacteria, including aminopenicillins, ureidopenicillins, cephalosporins, beta-lactam-betalactamase inhibitor combinations (such as piperacillin-tazobactam), folate antagonists, quinolones, and carbapenems. Many of these antibiotics also cover Gram-positive bacteria. The antibiotics that specifically target Gram-negative organisms include aminoglycosides, monobactams (such as aztreonam), and ciprofloxacin.

Conventional Gram-negative (LPS-diderm) bacteria display the following characteristics:^{[citation needed]}

However, the LPS-diderm group (corresponding to kingdom Pseudomonadati, formerly "Hydrobacteria") is not the only type of bacteria that stain negative. Mycobacterium (or rather most of Mycobacteriales), which does not belong in the group, have independently evolved an outer cell membrane, with a cell wall made of mycolic acid. This gives it very different structure and features.

In many Gram-negative bacteria, the IgaA membrane protein negatively regulates the Rcs phosphorelay system, a key envelope stress response pathway that helps maintain cell envelope integrity.

Along with cell shape, Gram staining is a rapid diagnostic tool and once was used to group species at the subdivision of Bacteria. Historically, the kingdom Monera was divided into four divisions based on Gram staining: Firmicutes (+), Gracillicutes (−), Mollicutes (0) and Mendocutes (var.). Since 1987, the monophyly of the Gram-negative bacteria has been disproven with molecular studies.

Current knowledge divides the Gram-negatives into two large groups and some straddlers. The more "conventional" Gram-negatives with an LPS outer membrane do share a common ancestor and are grouped in kingdom Pseudomonadati. The less conventional ones are, as mentioned above, the order Mycobacteriales, have a mycolic acid cell wall and an outer membrane. The kingdom and the order are each monophyletic (or rather, not holyphyletic), but the "LPS-diderm" and "mycolic-diderm" groups are not, because some bacteria in the kingdom and the order do not, in fact, stain Gram negative. They will be discussed in the next section.