Gram-negative cocci

The Gram stain separates bacteria by cell wall structure. Gram-positive organisms have a thick peptidoglycan layer that traps the crystal violet–iodine complex and appears purple; gram-negative organisms have a thin peptidoglycan layer sandwiched between an inner and an outer membrane, lose the primary stain during decolorization, and take up the pink safranin counterstain. Combining that result with cell shape gives the four basic buckets, and the gram-negative cocci are by far the smallest of them — a short list worth memorizing outright.

The genus that matters most is Neisseria, gram-negative diplococci often described as kidney-bean or coffee-bean shaped and classically seen inside neutrophils on clinical specimens. Both pathogenic species are oxidase positive and grow on chocolate agar and on selective Thayer-Martin medium. The standard sugar-fermentation mnemonic separates them: *N. meningitidis* ferments both maltose and glucose, while *N. gonorrhoeae* ferments glucose only. *Moraxella catarrhalis* is the other commonly tested organism in the group, a gram-negative diplococcus that is a frequent cause of otitis media, sinusitis, and exacerbations of chronic obstructive pulmonary disease.

Clinically the two Neisseria species behave very differently. *N. meningitidis* is encapsulated, spreads by respiratory droplets, colonizes the nasopharynx, and causes meningitis and fulminant meningococcemia — including adrenal hemorrhage in Waterhouse-Friderichsen syndrome. It affects crowded populations such as college dormitories and military recruits, and vaccines target its capsular polysaccharides — except the serogroup B vaccines, which use surface proteins because the type B capsule is poorly immunogenic. *N. gonorrhoeae* has no protective capsule and no effective vaccine, is sexually transmitted, and causes urethritis, cervicitis, pelvic inflammatory disease, septic arthritis, and neonatal conjunctivitis acquired during delivery. Its antigenic variation of pili is a major reason reinfection is common. Both species share IgA protease as a virulence factor and lipooligosaccharide endotoxin.

USMLE Step 1 microbiology tests this group as a discrete category, and the reliable question stems are the maltose fermentation difference, capsule versus no capsule, and matching each organism to its classic clinical presentation.