Antibiotic-induced filamentation Some
peptidoglycan synthesis inhibitors (e.g.
cefuroxime,
ceftazidime) induce filamentation by inhibiting the
penicillin binding proteins (PBPs) responsible for crosslinking peptidoglycan at the septal wall (e.g. PBP3 in
E. coli and
P. aeruginosa). Because the PBPs responsible for lateral wall synthesis are relatively unaffected by cefuroxime and ceftazidime, cell elongation proceeds without any cell division and filamentation is observed.
DNA synthesis-inhibiting and DNA damaging antibiotics (e.g.
metronidazole,
mitomycin C, the
fluoroquinolones,
novobiocin) induce filamentation via the
SOS response. The SOS response inhibits septum formation until the DNA can be repaired, this delay stopping the transmission of damaged DNA to progeny. Bacteria inhibit septation by synthesizing protein SulA, an
FtsZ inhibitor that halts Z-ring formation, thereby stopping recruitment and activation of PBP3. If bacteria are deprived of the
nucleobase thymine by treatment with
folic acid synthesis inhibitors (e.g.
trimethoprim), this also disrupts DNA synthesis and induces SOS-mediated filamentation. Direct obstruction of Z-ring formation by SulA and other FtsZ inhibitors (e.g.
berberine) induces filamentation too. Some
protein synthesis inhibitors (e.g.
kanamycin),
RNA synthesis inhibitors (e.g.
bicyclomycin) and membrane disruptors (e.g.
daptomycin,
polymyxin B) cause filamentation too, but these filaments are much shorter than the filaments induced by the above antibiotics. low water availability, high osmolarity, extreme pH, and UV exposure. UV light damages bacterial DNA and induces filamentation via the
SOS response. Starvation can also cause bacterial filamentation.
Nutrient-induced filamentation Several macronutrients and biomolecules can cause bacterial cells to filament, including the amino acids glutamine, proline and arginine, and some branched-chain amino acids. Certain bacterial species, such as
Paraburkholderia elongata, will also filament as a result of a tendency to accumulate phosphate in the form of polyphosphate, which can chelate metal cofactors needed by division proteins.
Intrinsic dysbiosis-induced filamentation Filamentation can also be induced by other pathways affecting
thymidylate synthesis. For instance, partial loss of
dihydrofolate reductase (DHFR) activity causes reversible filamentation. DHFR has a critical role in regulating the amount of
tetrahydrofolate, which is essential for
purine and thymidylate synthesis. DHFR activity can be inhibited by
mutations or by high concentrations of the antibiotic
trimethoprim (see antibiotic-induced filamentation above). Overcrowding of the periplasm or envelope can also induce filamentation in Gram-negative bacteria by disrupting normal divisome function.
Filamentation and biotic interactions Several examples of filamentation that result from biotic interactions between bacteria and other organisms or infectious agents have been reported. Filamentous cells are resistant to ingestion by bacterivores, and environmental conditions generated during predation can trigger filamentation. Filamentation can also be induced by signalling factors produced by other bacteria. In addition,
Agrobacterium spp. filament in proximity to plant roots, and
E. coli filaments when exposed to plant extracts. Lastly, bacteriophage infection can result in filamentation via the expression of proteins that inhibit divisome assembly. == See also ==