Filamentation
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Filamentation is the anomalous growth of certain
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
, such as ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'', in which cells continue to elongate but do not divide (no
septa The Southeastern Pennsylvania Transportation Authority (SEPTA) is a regional public transportation authority that operates bus, rapid transit, commuter rail, light rail, and electric trolleybus services for nearly 4 million people in five coun ...
formation). The cells that result from elongation without division have multiple chromosomal copies. In the absence of
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s or other stressors, filamentation occurs at a low frequency in bacterial populations (4–8% short filaments and 0–5% long filaments in 1- to 8-hour cultures). The increased cell length can protect bacteria from
protozoa Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
n
predation Predation is a biological interaction where one organism, the predator, kills and eats another organism, its prey. It is one of a family of common feeding behaviours that includes parasitism and micropredation (which usually do not kill the ...
and
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
phagocytosis by making
ingestion Ingestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in a substance through the mouth into the gastrointestinal tract, such as through eating or drinking. In single-celled organisms ingest ...
of cells more difficult. Filamentation is also thought to protect bacteria from antibiotics, and is associated with other aspects of bacterial
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...
such as
biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...
formation. The number and length of filaments within a bacterial population increases when the bacteria are exposed to different physical, chemical and biological agents (e.g.
UV light Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30  PHz) to 400 nm (750  THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
, DNA synthesis-inhibiting antibiotics,
bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...
s). This is termed conditional filamentation. Some of the key genes involved in filamentation in ''E. coli'' include ''sulA'' and ''minCD''.


Filament formation


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 Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is ef ...
, mitomycin C, the
fluoroquinolones A quinolone antibiotic is a member of a large group of broad-spectrum antibiotic, broad-spectrum bacteriocidals that share a bicyclic molecule, bicyclic core structure related to the substance 4-Quinolone, 4-quinolone. They are used in human and ...
,
novobiocin Novobiocin, also known as albamycin or cathomycin, is an aminocoumarin antibiotic that is produced by the actinomycete '' Streptomyces niveus'', which has recently been identified as a subjective synonym for ''S. spheroides'' a member of the clas ...
) 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 Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic b ...
thymine Thymine () ( symbol T or Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nu ...
by treatment with
folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
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 Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as ''Berberis vulgaris'' (barberry), ''Berberis aristata'' (tree turmeric), ''Mahonia aquifolium'' (Oregon grape), ''Hydra ...
) induces filamentation too. Some
protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
inhibitors (e.g. kanamycin), RNA synthesis inhibitors (e.g.
bicyclomycin Bicyclomycin (Bicozamycin) is a broad spectrum antibiotic active against Gram-negative bacteria and the Gram-positive bacterium, ''Micrococcus luteus'' that was isolated from ''Streptomyces sapporonesis'' and ''Streptomyces aizumenses'' in 1972. ...
) 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.


Stress-induced filamentation

Filamentation is often a consequence of environmental stress. It has been observed in response to temperature shocks, 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. For example, if bacteria are deprived of the nucleobase thymine, this disrupts DNA synthesis and induces SOS-mediated 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 ''Paraburkholderia elongata'' is a Gram-negative bacteria, Gram-negative bacterium belonging to the genus ''Paraburkholderia''. The type strain is ''P. elongata'' 5NT, which was isolated from the Arnot research forest, near Van Etten, New York, u ...
'', 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. In addition, filamentation is induced by nutrient-rich conditions in the intracellular pathogen ''
Bordetella atropi ''Bordetella'' () is a genus of small (0.2 – 0.7 µm), gram-negative coccobacilli of the phylum Pseudomonadota. ''Bordetella'' species, with the exception of '' B. petrii'', are obligate aerobes, as well as highly fastidious, or difficult ...
''. This occurs via the highly conserved UDP-glucose pathway. UDP-glucose biosynthesis and sensing suppresses bacterial cell division, with the ensuing filamentation allowing ''B. atropi'' to spread to neighboring cells.


Intrinsic dysbiosis-induced filamentation

Filamentation can also be induced by other pathways affecting
thymidylate Thymidine monophosphate (TMP), also known as thymidylic acid (conjugate base thymidylate), deoxythymidine monophosphate (dTMP), or deoxythymidylic acid (conjugate base deoxythymidylate), is a nucleotide that is used as a monomer in DNA. It is an ...
synthesis. For instance, partial loss of
dihydrofolate reductase Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. In ...
(DHFR) activity causes reversible filamentation. DHFR has a critical role in regulating the amount of tetrahydrofolate, which is essential for
purine Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which includ ...
and thymidylate synthesis. DHFR activity can be inhibited by
mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
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

* Bacterial morphological plasticity * Filamentous bacteriophage * Filamentous cyanobacteria *
Segmented filamentous bacteria Segmented filamentous bacteria or ''Candidatus'' Savagella are members of the gut microbiota of rodents, fish and chickens, and have been shown to potently induce immune responses in mice. They form a distinct lineage within the Clostridiaceae a ...


References

{{Reflist, 2 Cellular processes Microbiology