Upon their activation, macrophages produce superoxide (O2−) and hydrogen peroxide (H2O2). Thus N. meningitidis is likely to encounter oxidative stress during its life cycle. Consequently, an important benefit of genetic transformation to N. meningitidis may be the maintenance of the recombination and repair machinery of the cell that removes oxidative DNA damages such as those caused by reactive oxygen. This is consistent with the more general idea that transformation benefits bacterial pathogens by facilitating repair of DNA damages produced by the oxidative defenses of the host during infection.Meningococci population is extensively diverse genetically, this is due to horizontal gene transfers while in the nasophanrynx. Gene transfer can occur within and between genomes of Neisseria species, and it is the main mechanism of acquiring new traits. This is facilitated by the natural competence of the meningococci to take up foreign DNA. The commensal species of Neisseria can act as a reservoir of genes that can be acquired, for example, this is how capsule switching can occur as a means of hiding from the immune system. An invasive N. meningitidis strain of serogroup C broke out in Nigeria in 2013 - the strain was a new sequence type, ST-10217 determined by multilocus sequence typing. It was determined that a commensal strain of N. meningitidis acquired an 8-kb prophage, the meningococcal disease-associated island (MDAΦ), previously associated with hyper-invasiveness; and the full serogroup C capsule operon, thus becoming a hypervirulent strain.
A single abnormal copy (heterozygote) of FH causes cardiovascular disease by the age of 50 in about 40% of cases. Having two abnormal copies (homozygote) causes accelerated atherosclerosis in childhood, including its complications. The plasma LDL levels are inversely related to the activity of LDL receptor (LDLR). Homozygotes have LDLR activity of less than 2%, while heterozygotes have defective LDL processing with receptor activity being 2–25%, depending on the nature of the mutation. Over 1000 different mutations are known.There are five major classes of FH due to LDLR mutations:
Class I: LDLR is not synthesized at all. Class II: LDLR is not properly transported from the endoplasmic reticulum to the Golgi apparatus for expression on the cell surface. Class III: LDLR does not properly bind LDL on the cell surface because of a defect in either apolipoprotein B100 (R3500Q) or in LDL-R.
Class IV: LDLR bound to LDL does not properly cluster in clathrin-coated pits for receptor-mediated endocytosis (pathway step 2). Class V: LDLR is not recycled back to the cell surface (pathway step 5). Apolipoprotein B
Apolipoprotein B, in its ApoB100 form, is the main apolipoprotein, or protein part of the lipoprotein particle. Its gene is located on the second chromosome (2p24-p23) and is 46.2 kb long. FH is often associated with the mutation of R3500Q, which causes replacement of arginine by glutamine at position 3500. The mutation is located on a part of the protein that normally binds with the LDL receptor, and binding is reduced as a result of the mutation.