Some bacteria (e.g. Salmonella typhi, Yersinia pestis, Rickettsiae, Mycobacteria) are known to penetrate and grow in the intracellular spaces inside host cells. What advantage does this environment have for the bacterium?
The quick answer is that being inside host cells allows bacteria to avoid the humoral immune response of the host, because the immune system does not attack inside host cells.
Salmonella, Yersinia, Shigella and Listeria monocytogenes "have the capacity to induce their own uptake into mammallian cells which are normally nonphagocytic." (Perspective Series, Host/Pathogen Interactions, Subversion of the Mammalian Cell Cytoskeleton by Invasive Bacteria by Pascale Cossart)
This suggests to me that the host cell uptake of Rickettsiae and Mycobacteria is by normally phagocytic cells.
It also seems apparent that once inside the host cell the bacteria benefit from the nutrients and supplies that are kept there for cellular metabolism, and can pilfer as needed to reproduce and grow.
ORGANISMS LISTED THAT GET INSIDE HOST CELLS:
Salmonella typhi. Gram-negative rod. Causes typhoid fever. Salmonella Typhi is a serovar of Salmonella enterica (formerly known as Salmonella choleraesuis). Fecal-oral transmission. Three main antigenic factors: the O, or somatic antigen; the Vi, or encapsulation antigen; and the H, or flagellar antigen. September 23, 1869 – November 11, 1938 Typhoid Mary Mallon was a healthy carrier. As a cook, she infected 47 people, three of whom died from the disease. It is possible she was born with the disease, as her mother had typhoid fever during her pregnancy.
Yersinia pestis. Gram-negative bacillus. Facultative anaerobic bipolar-staining (giving it a safety pin appearance). Infectious agent of bubonic plague, also pneumonic and septicemic plague. All three forms have high mortality rates in epidemics incl the Black Death (~1/3 of the European population died 1347 to 1353). Fermentative metabolism. Produces an antiphagocytic slime. Organism is motile when isolated, but becomes nonmotile in a mammalian host. Tx: streptomycin, chloramphenicol, tetracycline, fluoroquinolones. Also poss: doxycycline or gentamicin.
Rickettsiae. Non-motile, Gram-negative, non-sporeforming, highly pleomorphic bacteria that can present as cocci (0.1 μm in diameter), rods (1-4 μm long) or thread-like (10 μm long). Obligate intracellular parasites: Rickettsia depend on entry, growth, and replication within the cytoplasm of eukaryotic host cells (typically endothelial cells). Usu grown in chicken embryos. Majority of Rickettsia susceptible to tetracyclines. Carried as parasites by ticks, fleas, and lice. Cause: typhus, rickettsialpox, Boutonneuse fever, African Tick Bite Fever, Rocky Mountain spotted fever, Australian Tick Typhus, Flinders Island Spotted Fever and Queensland Tick Typhus in human beings, also plant diseases. Thought to be the closest living relatives to pre-mitochondrial bacteria. ATP production in Rickettsia is the same as that in mitochondria.
Mycobacteria. Usu considered gram positive 'cause lacks an outer cell membrane.. Aerobic and nonmotile except M. marinum which is motile inside macrophages. Acid-alcohol fast. No endospores or capsules. Genus: Actinobacteria, family: Mycobacteriaceae. Incl pathogens causing tuberculosis and leprosy. The tuberculosis and the leprosy organisms appear to be obligate parasites. Latin prefix "myco—" means both fungus and wax; here relates to "waxy" compounds in the thick cell wall, rich in mycolic acids. Some sp. fastidious. Asymptomatic TB infx is common. Hard to treat, resistant to penicillin. LOTS of species!!
MORE ORGS THAT GET INSIDE HOST CELLS:
Listeria monocytogenes. Gram positive rod. Tumbling motility. Intracellular growth at low temperatures. Virulence factors that facilitate host cell invasion: Listeriolysin O and Internalin. Internalin binds to the host cell and promotes endocytosis. Listeriolysin O forms a pore that lets the organism escape from the endosome. It can spread from cell to cell, further evading the humoral immune response. Can spread from mother to child via placenta. Immune clearance requires a T-cell response. S/sx: fetal meningitis, pneumonia or septicemia, adults may be asymptomatic, or get bacterial meningitis (usu only immune compromised individuals). Tx: aminoglycosides, trimethoprimsulfamethoxazole, ampilcillin.
Shigella. Gram-negative, non-motile, non-spore forming rod-shaped bacteria. Closely related to Escherichia coli and Salmonella. Causes: human shigellosis, and disease in other primates. Four serogroups: A: dysenteriae, B: flexneri, C: boydii, D: sonnei. Transmission: fecal-oral. Dysentery that results in the destruction of the epithelial cells of the intestinal mucosa in the cecum and rectum. Some strains produce enterotoxin and Shiga toxin, similar to the verotoxin of E. coli O157:H7. Both Shiga toxin and verotoxin are associated with causing hemolytic uremic syndrome. S/sx: diarrhea, fever, nausea, vomiting, stomach cramps, and straining to have a BM. Stool may contain blood, mucus, or pus. Rare: young children may have seizures. Symptoms can take as long as a week to show up, but usu begin two to four days after ingestion. Symptoms usually last for several days, but can last for weeks. Shigella is implicated as one of the pathogenic causes of reactive arthritis worldwide. Tx: ampicillin, TMP-SMX, or fluoroquinolones such as ciprofloxacin.
Shigella invade the host through epithelial cells of the large intestine. Using a Type III secretion system acting as a biological syringe, the bacterium injects IpaD protein into cell, triggering bacterial invasion and the subsequent lysis of vacuolar membranes using IpaB and IpaC proteins. It utilizes a mechanism for its motility by which its IcsA protein triggers actin polymerization in the host cell (via N-WASP recruitment of Arp2/3 complexes) in a "rocket" propulsion fashion for cell-to-cell spread.
Shigella that have traversed M cells are then engulfed by underlying macrophages where they induce apoptosis. Apoptotoic macrophages release IL-1beta contributing to a severe inflammatory response. Bacteria released from dying cells can invade enterocytes through the basolateral surface.
MECHANISMS OF ENTRY:
note: even pathogens that share a common uptake strategy appear to target different host proteins to induce uptake.
Zipper type event. Yersinia and Listeria. Yersinia stays in membrane-bound vacuole. Listeria gets out and swims around. Yersinia pseudotuberculosis gets in via the intestine using INVASIN, a 986 aa outer membrane protein, the 192 carboxy-terminal aa's of which bind mammalian cells. Invasin is enough to get in a cell, because they got cells to swallow latex beads using it. Listeria innocua has INTERNALIN aka InlA, a surface protein that makes it invasive just like INVASIN on Yersinia. INTERNALIN has multiple tandem copies of a 22 aa leucine-rich motif called a leucine-rich repeat (LRR).
Trigger phenotype. Salmonella and Shigella. Salmonella stays in membrane-bound vacuole. Shigella lyses vacuaoles and moves in cytoplasm by polymerizing actin. Upon contact with host cell these bacteria trigger a dramatic rearrangement of cellular F-actin, characterized by large membrane projections similar to membrane ruffles induced by some graown factors or oncogenes. After 1 min it's happening, and the membrane region affected enlarges ofver 3 minutes and may lead to macropinocytosis and passive entry of anything trapped. The host membrane is not closely apposed to the bacterium but engulfs it in a large vacuole.