biofilm细菌矩阵

biofilm就是一个细菌矩阵，功能强大得如同航空母舰。一个生物膜可以有成百上千种细菌组成，生物膜对抗生素抗体是单个细菌的400倍，生物膜细菌群可以不用分裂而继续生存，并进行不同次级代谢；生物膜还具有群体感应，外界ph,抗生素等外部因素对其基本不起作用。下图是生物膜形成5个阶段。多么恐怖。。。

Oral microbiology is the study of the microorganisms of the oral cavity(腔) and theinteractions(相互作用) between the oral microorganisms(微生物) with each other and with the host. Of particular interest is the role of oral microorganisms in the two major dental(牙科的)diseases: dental caries and periodontal disease.^[1]

The mouth harbors a diverse(不同的), abundant(丰富的) and complex(复杂的) microbial(微生物的)community. This highly diverse microflora inhabits(栖息) the various surfaces of the normal mouth.Bacteria accumulate(累积) on both the hard and soft oral tissues(纸巾) in biofilms. Bacterialadhesion is particularly important for oral bacteria.

Oral bacteria have evolved(发展) mechanisms(机制) to sense their environment and evade(逃避) ormodify(修改) the host. Bacteria occupy(占据) the ecological(生态的) niche(壁龛) provided by both the tooth surface and gingival epithelium. However, a highly efficient(有效率的) innate(先天的)host defense system constantly monitors the bacterial(细菌的) colonization(殖民) and prevents bacterial invasion(入侵) of local tissues(纸巾). A dynamic(动态的) equilibrium(均衡) exists between dental plaque bacteria and the innate host defense system.^[1]

目录

• 1 Oral bacteria
  • 1.1 Fusospirochetes
  • 1.2 Veillonella
  • 1.3 Aggregatibacter actinomycetemcomitans
  • 1.4 Lactobacillus
• 2 Dental plaque
• 3 Cell-cell communication
• 4 Vaccination(接种疫苗) against oral infections(感染)
• 5 See also
• 6 References
• 7 External links

Oral bacteria

Oral bacteria include streptococci(链球菌), lactobacilli(乳酸杆菌), staphylococci(葡萄状球菌),corynebacteria(棒状杆菌), and various anaerobes in particular bacteroides. The oral cavity(腔) of the new-born baby does not contain bacteria but rapidly becomes colonized(移于殖民地) with bacteria such as Streptococcus salivarius. With the appearance of the teeth during the first yearcolonization(殖民) by Streptococcus mutans and Streptococcus sanguinis occurs as theseorganisms(有机体) colonise(开拓殖民地) the dental(牙科的) surface and gingiva(齿龈). Otherstrains(张力) of streptococci(链球菌) adhere(坚持) strongly to the gums(口香糖) and cheeks but not to the teeth. The gingival(齿龈的) crevice(裂缝) area (supporting structures(结构) of the teeth) provides a habitat(栖息地) for a variety of anaerobic(厌氧的) species(硬币). Bacteroides andspirochetes(螺旋体) colonize the mouth around puberty(青春期).^[1]

Fusospirochetes

Spirochetes and fusi-form bacilli(杆菌) live as normal flora(植物区系) in the mouth, but in the case of bleeding in the oral cavity, the bacteria can cause infection(感染) and diseases to oral cavity:

1. Acute(严重的) necrotizing(坏死) ulcerative(溃疡性的) gingivitis(齿龈炎) (ANUG)
2. Vincent angina(心绞痛) with a membrane(膜) covering the throat area

Veillonella

Veillonella are gram-negative anaerobic(厌氧的) cocci(球菌). It is thought that this species(物种)thrives(繁荣) in the acidic(酸的) environment of caries(龋齿) and is thought to slow the development of dental(牙科的) caries. It converts(皈依者) the acidic products of other species to less acidic products.

Aggregatibacter actinomycetemcomitans

Aggregatibacter actinomycetemcomitans is considered an oral pathogen(病原体) due to itsvirulence(毒力) factors(因素), its association(协会) with localized(局部的) aggressiveperiodontitis(牙周炎) in young adolescents(青少年), and studies indicating(表明) that it can cause bone loss.^[2]

Lactobacillus

Some Lactobacillus species(物种) have been associated(交往) with dental(牙科的) caries(龋齿)although these bacteria are normally symbiotic(共生的) in humans and are found in the gut flora(植物区系).^[3]

Dental plaque

Dental plaque(匾) is the material that adheres(坚持) to the teeth and consists of bacterial(细菌的) cells (mainly S. mutans and S. sanguis), salivary(唾液的) polymers(聚合物) and bacterialextracellular(细胞外的) products. Plaque is a biofilm(生物膜) on the surfaces of the teeth. Thisaccumulation(积聚) of microorganisms(微生物) subject the teeth and gingival(齿龈的) tissues(纸巾)to high concentrations(浓度) of bacterial metabolites(代谢物) which results in dental disease. If not taken care of, via brushing or flossing(用牙线洁牙), the plaque can turn into tartar (itshardened(变硬的) form) and lead to gingivitis(齿龈炎) or periodontal(齿根膜的) disease.

Cell-cell communication

Most of the bacterial species found in the mouth belong(属于) to microbial(微生物的) communities, called biofilms, a feature(特色) of which is inter-bacterial communication. Cell-cell contact ismediated(调解) by specific(特殊的) protein(蛋白质) adhesins and often, as in the case of inter-species aggregation(聚合), by complementary(补足的) polysaccharide(多糖) receptors(受体). Another method of communication involves(包含) cell-cell signalling(信号传输法) molecules(分子), which are of two classes: those used for intra-species and those used for inter-species signalling. An example of intra-species communication is quorum sensing. Oral bacteria have been shown to produce small peptides(缩氨酸), such as competence(能力) stimulating(刺激) peptides, which can helppromote(促进) single-species biofilm(生物膜) formation(形成). A common form of inter-species signalling is mediated by 4, 5-dihydroxy-2, 3-pentanedione (DPD) or Autoinducer-2 (Al-2).^[4]

Vaccination(接种疫苗) against oral infections(感染)

In the case of dental(牙科的) caries(龋齿), proteins involved in colonization(殖民) of teeth byStreptococcus mutans can produce antibodies that inhibit(抑制) the cariogenic process.^[5]

生物薄膜（英语：biofilm），也称作“生物膜”或“菌膜”，是一些微生物細胞由自身產生的胞外多聚物基質（主要爲多糖）所包圍而形成，且附著在浸有液體的惰性或生物表面的，具有結構的群落。

目录

• 1 重要性
• 2 特點
• 3 結構
• 4 形成
• 5 防止

重要性

生物膜在醫學、工業和生態上都具有重要意義。

在醫學中，人類大約65%的細菌性疾病有生物膜參與。如在口腔中，牙齒表面的生物膜可形成牙菌斑、齲齒和牙齦感染。生物膜也可導致器官移植後（如心臟起搏器）的感染。空調中的退伍軍人菌（Legionella pneumoniae）形成生物膜可導致退伍軍人病。綠膿桿菌(Pseudomonas aeruginosa)在肺部感染的形成囊性纖維變性、肺結核、尿路感染、呼吸道感染和大約25%的腎結石也是由生物膜造成的。

輸油管道中形成的生物膜會嚴重影響管道輸送能力。

特點

生物膜中的細胞和游離細胞有很多不同點：

• 生物膜中的細菌對抗生素、過氧化氫或者去污劑的抗性比游離細胞高可達400倍。
• 通過二維蛋白質電泳，發現生物膜中的細菌可能表達40%和游離細胞不同的蛋白。
• 生物膜中的細菌可以不分裂而維持生存（休眠）很長時間。
• 生物膜中的生物合成更多的向外分泌的多糖，並進行不同的次級代謝。
• 生物膜中的細菌對外界環境條件改變（如pH、離子濃度、滲透壓、黏度、營養、氣體交換）作出的反應更迅速。

結構

生物膜體積的90%由聚合物基質或水管道構成。生物膜具有結構而非均一，管道可用於生物膜内部的細菌交換物質。生物膜中，構成底層和表層的細菌種類和比例也不同。

生物膜的細胞可通過群體感應（quorum sensing）調整自身的生理狀況。

形成

生物薄膜的形成过程

生物膜的形成有以下步驟：

1. 細菌的可逆吸附（秒）
2. 細菌的不可逆附著，改變被附著表面的特性，使其更易被附著（秒~分）
3. 細菌的生長和分裂（小時~天）
4. 胞外聚合物的產生，生物膜開始形成（小時~天）
5. 其他生物在生物膜上的附著（天~月）

防止

爲防止某些情況下的生物膜形成，有如下辦法：

預防性：

• 防止營養物沉積
• 特殊的表面使細菌無法附著（“荷葉效應”）

物理方法：

• 超聲
• 高電壓
• 磁場

化學方法：

• 抗生素
• 去污劑
• 過氧化氫
• 螯合劑（如EDTA）

生物調控方法：

• 加入群體感性中誘導物的相似物質從而抑制群體感應

A biofilm is any group of microorganisms in which cells stick to each other on a surface. Theseadherent(信徒) cells are frequently embedded(栽种) within a self-produced matrix(矩阵) ofextracellular polymeric substance(物质) (EPS). Biofilm(生物膜) EPS, which is also referred to asslime (although not everything described as slime is a biofilm), is a polymeric conglomeration(聚集) generally composed(构成) of extracellular(细胞外的) DNA, proteins, and polysaccharides.Biofilms(生物膜) may form on living or non-living surfaces and can be prevalent(流行的) in natural, industrial(工业股票) and hospital settings.^[2][3] The microbial(微生物的) cells growing in a biofilm are physiologically distinct from planktonic cells of the same organism(有机体), which, by contrast(对比), are single-cells that may float or swim in a liquid medium(方法).

Microbes(细菌) form a biofilm in response to many factors(因素), which may include cellular(细胞的) recognition(识别) of specific(特殊的) or non-specific(不明确的) attachment(附件) sites on a surface, nutritional(营养的) cues(提示), or in some cases, by exposure(暴露) of planktonic(浮游生物的) cells to sub-inhibitory concentrations(浓度) of antibiotics(抗生素).^[4][5] When a cellswitches(开关) to the biofilm(生物膜) mode of growth, it undergoes(经历) a phenotypic shift(移动)in behavior(行为) in which large suites of genes are differentially(微分的) regulated.^[6]

目录

• 1 Formation
• 2 Development
• 3 Dispersal
• 4 Properties
  • 4.1 Extracellular matrix
• 5 Examples
• 6 Biofilms(生物膜) and infectious(传染的) diseases
  • 6.1 Dental plaque
  • 6.2 Legionellosis
• 7 See also
• 8 References
• 9 Further reading
• 10 External links

Formation

Formation(形成) of a biofilm(生物膜) begins with the attachment(附件) of free-floatingmicroorganisms(微生物) to a surface. These first colonists(殖民者) adhere(坚持) to the surface initially through weak, reversible(可逆的) adhesion(粘附) via van der Waals forces. If the colonists are not immediately separated from the surface, they can anchor(抛锚) themselves morepermanently(永久地) using cell adhesion structures such as pili.^[7] Hydrophobicity also plays an important role in determining the ability of bacteria to form biofilms, as those with increasedhydrophobicity(疏水性) have reduced repulsion(排斥) between the extracellular matrix and the bacterium.^[8] Some species(物种) are not able to attach(依附) to a surface on their own but are sometimes able to anchor(抛锚) themselves to the matrix(矩阵) or directly to earlier colonists(殖民者). It is during this colonization(殖民) that the cells are able to communicate via quorum sensing using products such as AHL. Some bacteria are unable to form biofilms(生物膜) as successfully due to their limited motility(运动性). Nonmotile(无运动的) bacteria cannot recognize the surface or aggregate(集合) together as easily as motile(能动的) bacteria.^[9] Once colonization has begun, the biofilm grows through a combination(结合) of cell division and recruitment(补充).Polysaccharide matrices(矩阵) typically(典型的) enclose(围绕) bacterial(细菌的) biofilms. In addition to the polysaccharides(多糖), these matrices may also contain material from the surrounding environment, including but not limited to minerals, soil particles(颗粒), and bloodcomponents(成分), such as erythrocytes(红细胞) and fibrin(纤维蛋白).^[10] The final stage of biofilm formation(形成) is known as dispersion(散布), and is the stage in which the biofilm isestablished(确定的) and may only change in shape and size. The development of a biofilm may allow for an aggregate cell colony(殖民地) (or colonies) to be increasingly antibiotic(抗生的)resistant(抵抗者).

Development

Five stages of biofilm(生物膜) development: (1) Initial attachment(附件), (2) Irreversible attachment, (3) Maturation I, (4) Maturation II, and (5) Dispersion. Each stage of development in the diagram is paired with a photomicrograph(显微照片) of a developing P. aeruginosa biofilm. All photomicrographs are shown to same scale(规模).

There are five stages of biofilm development (see illustration(说明) at right):

1. Initial attachment:
2. Irreversible attachment:
3. Maturation I:
4. Maturation II:
5. Dispersion:

Dispersal

Dispersal(分散) of cells from the biofilm colony(殖民地) is an essential stage of the biofilm life cycle. Dispersal enables biofilms to spread and colonize(移于殖民地) new surfaces. Enzymes(酶)that degrade(贬低) the biofilm(生物膜) extracellular(细胞外的) matrix(矩阵), such as dispersin Band deoxyribonuclease, may play a role in biofilm dispersal(分散).^[11][12] Biofilm matrixdegrading(贬低) enzymes(酶) may be useful as anti-biofilm agents.^[13][14] Recent evidence(证据)has shown that a fatty(胖子) acid(酸) messenger(报信者), cis-2-decenoic acid, is capable(能干的)of inducing(产生诱导作用的) dispersion(散布) and inhibiting(抑制作用的) growth of biofilm(生物膜)colonies(殖民地). Secreted(分泌) by Pseudomonas aeruginosa, this compound(复合的) induces cyclo(三轮车) heteromorphic(异形的) cells in several species(物种) of bacteria and the yeast(酵母) Candida albicans.^[15] Nitric(氮的) oxide(氧化物) has also been shown to trigger(引发) the dispersal(分散)of biofilms of several bacteria species ^[16][17] at sub-toxic concentrations(浓度). Nitric oxidehas the potential(潜能) for the treatment of patients that suffer from chronic(慢性的)infections(感染) caused by biofilms.^[18]

Properties

Biofilms(生物膜) are usually found on solid substrates submerged(水下的) in or exposed to anaqueous solution, although they can form as floating mats on liquid surfaces and also on the surface of leaves, particularly in high humidity(湿度) climates. Given sufficient(足够的)resources for growth, a biofilm will quickly grow to be macroscopic(宏观的) (visible(可见物) to the naked(裸体的) eye). Biofilms can contain many different types of microorganism(微生物), e.g.bacteria, archaea, protozoa, fungi and algae; each group performs specialized(专门从事) metabolicfunctions. However, some organisms(有机体) will form single-species films under certain conditions. The social structure(结构) (cooperation(合作), competition) within a biofilm(生物膜)highly depends on the different species(物种) present.^[19]

Extracellular matrix

The biofilm is held together and protected by a matrix(矩阵) of secreted(分泌) polymericcompounds(化合物) called EPS. EPS is an abbreviation(缩写) for either extracellular(细胞外的)polymeric(聚合的) substance(物质) or exopolysaccharide. This matrix protects the cells within it and facilitates(促进) communication among them through biochemical(生物化学的) signals. Some biofilms have been found to contain water channels that help distribute(分配) nutrients and signalling molecules.^[20] This matrix(矩阵) is strong enough that under certain conditions,biofilms(生物膜) can become fossilized (Stromatolites).

Bacteria living in a biofilm usually have significantly(意味深长地) different properties from free-floating bacteria of the same species(物种), as the dense(稠密的) and protected environment of the film allows them to cooperate(合作) and interact(互相影响) in various ways. One benefit(利益) of this environment is increased resistance(阻力) to detergents and antibiotics, as the denseextracellular(细胞外的) matrix and the outer layer of cells protect the interior(内部) of the community. In some cases antibiotic(抗生的) resistance can be increased a thousandfold(千倍地).^[21] Lateral gene transfer is greatly facilitated(促进) in biofilms and leads to a more stable(马厩) biofilm structure(结构).^[22]

However, biofilms(生物膜) are not always less susceptible(易受影响的) to antibiotics(抗生素). Forinstance(举…为例), the biofilm form of Pseudomonas aeruginosa has no greater resistance(阻力) toantimicrobials(抗菌剂) than do stationary-phase planktonic(浮游生物的) cells, although when the biofilm is compared to logarithmic(对数的) phase(相) planktonic cells, the biofilm does have greater resistance to antimicrobials. This resistance to antibiotics in both stationary(固定的)phase cells and biofilms may be due to the presence(存在) of persister cells.^[23]

Examples

Biofilm in Yellowstone National Park. Longest raised mat area is about half a meter long.

Thermophilic(适温的) bacteria in the outflow(流出) of Mickey Hot Springs, Oregon,approximately(大约) 20 mm thick.

Biofilms(生物膜) are ubiquitous(普遍存在的). Nearly every species(物种) of microorganism(微生物), not only bacteria and archaea(古生菌), have mechanisms(机制) by which they can adhere(坚持) to surfaces and to each other. Biofilms will form on virtually(事实上) every non-shedding surface in a non-sterile aqueous(水的) (or very humid(潮湿的)) environment.

• Biofilms can be found on rocks and pebbles(卵石) at the bottom of most streams or rivers and often form on the surface of stagnant pools of water. In fact, biofilms are importantcomponents(成分) of food chains in rivers and streams and are grazed(擦破的) by the aquatic(水生的) invertebrates upon which many fish feed.
• Biofilms can grow in the most extreme(极端的) environments: from, for example, the extremely hot, briny(海水的) waters of hot springs ranging from very acidic(酸的) to very alkaline(碱性的), to frozen glaciers.
• In the human environment, biofilms can grow in showers very easily since they provide amoist(潮湿) and warm environment for the biofilm to thrive(繁荣). Biofilms can form inside water and sewage(污水) pipes and cause clogging(堵塞) and corrosion. Biofilms(生物膜) on floors and counters can make sanitation(环境卫生) difficult in food preparation areas.
• Biofilms in cooling- or heating-water systems are known to reduce heat transfer(转让).^[24]
• Biofilms in marine(船舶的) engineering systems, such as pipelines(管道) of the offshore oil and gas industry,^[25] can lead to substantial(大量的) corrosion(腐蚀) problems. Corrosion is mainly due to abiotic(非生物的) factors(因素); however, at least 20% of corrosion is caused bymicroorganisms(微生物) that are attached(依附) to the metal subsurface(地表下岩石) (i.e.,microbially(微生物的) influenced corrosion).
• Bacterial(细菌的) adhesion(粘附) to boat hulls(船体) serves as the foundation(基础) forbiofouling of seagoing(适于远航的) vessels(船). Once a film of bacteria forms, it is easier for other marine organisms(有机体) such as barnacles(藤壶) to attach. Such fouling(污染) can reduce maximum vessel speed by up to 20%, prolonging(延长) voyages and consuming(消费的) fuel. Time in dry dock(码头) for refitting(改装) and repainting(重新绘制) reduces theproductivity(生产力) of shipping assets(资产), and the useful life of ships is also reduced due to corrosion and mechanical(机械的) removal(免职) (scraping(刮)) of marine organisms from ships‘ hulls.
• Biofilms can also be harnessed(治理) for constructive(建设性的) purposes. For example, manysewage treatment plants include a treatment stage in which waste water passes over biofilms grown on filters, which extract(汁) and digest organic(有机的) compounds(化合物). In such biofilms, bacteria are mainly responsible(负责的) for removal of organic matter (BOD), whileprotozoa and rotifers are mainly responsible(负责的) for removal(免职) of suspended(悬浮的)solids (SS), including pathogens(病原体) and other microorganisms(微生物). Slow sand filtersrely(依靠) on biofilm(生物膜) development in the same way to filter surface water from lake, spring or river sources for drinking purposes. What we regard as clean water is effectively(有效地) a waste material to these microcellular organisms(有机体).
• Biofilms can help eliminate(消除) petroleum oil from contaminated(受污染的) oceans ormarine(船舶的) systems. The oil is eliminated by the hydrocarbon-degrading activities ofmicrobial(微生物的) communities, in particular by a remarkable(卓越的) recently discovered group of specialists, the so-called hydrocarbonoclastic bacteria (HCB).^[26]
• Stromatolites are layered accretionary structures(结构) formed in shallow water by the trapping, binding(结合) and cementation(黏结) of sedimentary(沉淀的) grains by microbial biofilms, especially of cyanobacteria. Stromatolites(叠层) include some of the most ancient records of life on Earth, and are still forming today.
• Biofilms(生物膜) are present on the teeth of most animals as dental plaque, where they may cause tooth decay and gum disease.
• Biofilms are found on the surface of and inside plants. They can either contribute(贡献) to crop disease or, as in the case of nitrogen-fixing Rhizobium on roots, exist symbiotically with the plant.^[27] Examples of crop diseases related to biofilms include Citrus Canker,Pierce‘s Disease of grapes, and Bacterial Spot of plants such as peppers and tomatoes.^[28]
• Biofilms(生物膜) are used in microbial fuel cells (MFCs) to generate(形成) electricity from a variety of starting materials, including complex(复杂的) organic(有机的) waste andrenewable(可再生的) biomass(生物量).^[3]

Biofilms and infectious(传染的) diseases

Biofilms have been found to be involved(包含) in a wide variety of microbial(微生物的)infections(感染) in the body, by one estimate(估计) 80% of all infections.^[29] Infectious processes in which biofilms have been implicated(暗示) include common problems such as urinary tract infections, catheter infections, middle-ear infections, formation of dental plaque,^[30]gingivitis,^[30] coating contact lenses,^[31] and less common but more lethal(致命的) processes such as endocarditis, infections in cystic fibrosis, and infections(感染) of permanent(永久的)indwelling(存在于…之中) devices(装置) such as joint(关节) prostheses and heart valves.^[32][33]More recently it has been noted that bacterial(细菌的) biofilms(生物膜) may impair(损害)cutaneous(皮肤的) wound healing and reduce topical(局部的) antibacterial(抗菌剂) efficiency(效率)in healing or treating infected(被感染的) skin wounds.^[34]

It has recently been shown that biofilms are present on the removed tissue(纸巾) of 80% of patients undergoing(经历) surgery(外科) for chronic(慢性的) sinusitis. The patients with biofilms were shown to have been denuded(剥夺) of cilia and goblet cells, unlike the controls withoutbiofilms(生物膜) who had normal cilia(纤毛) and goblet(酒杯) cell morphology(形态学).^[35] Biofilms were also found on samples(样品) from two of 10 healthy controls mentioned. The species(物种) of bacteria from interoperative cultures did not correspond to the bacteria species in the biofilm on the respective(分别的) patient‘s tissue(纸巾). In other words, the cultures were negative(负的)though the bacteria were present.^[36]

Biofilms can also be formed on the inert(惰性的) surfaces of implanted(种植) devices(装置) such ascatheters(导管), prosthetic(假体的) cardiac(心脏的) valves(阀) and intrauterine(子宫内的) devices.^[37]

New staining(着色) techniques are being developed to differentiate(区分) bacterial(细菌的) cells growing in living animals, e.g. from tissues with allergy-inflammations .^[38]

Research has shown that sub-therapeutic levels of β-lactam antibiotics(抗生素) induce(诱导)biofilm formation(形成) in Staphylococcus aureus. This sub-therapeutic level of antibiotic(抗生素)may result from the use of antibiotics as growth promoters(促进) in agriculture, or during the normal course of antibiotic therapy(治疗). The biofilm(生物膜) formation(形成) induced(诱导) by low-level methicillin(甲氧西林) was inhibited(抑制) by DNase, suggesting that the sub-therapeutic levels of antibiotic also induce extracellular(细胞外的) DNA release.^[39]

Dental plaque

Dental plaque is an oral biofilm that adheres(坚持) to the teeth and consists of many species(物种) of both fungal(真菌的) and bacterial(细菌的) cells (such as Streptococcus mutans and Candida albicans), salivary polymers and microbial(微生物的) extracellular products. The accumulation(积聚) of microorganisms(微生物) subjects the teeth and gingival(齿龈的) tissues(纸巾) to highconcentrations(浓度) of bacterial metabolites which results in dental(牙科的) disease.^[30][40]

Legionellosis

Legionella bacteria are known to grow under certain conditions in biofilms(生物膜), in which they are protected against disinfectants. Workers in cooling towers, persons working in air conditioned rooms and people taking a shower are exposed to Legionella by inhalation(吸入) when the systems are not well designed, constructed, or maintained(维持).^[41]