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REZUMAT
Biofilmul microbian este un agregat de microorganisme care se poate forma pe suprafee vii sau non-vii, i
poate fi rspndit pretutindeni n natur.
Procesele infecioase comune n care au fost implicate biofilme includ infeciile tractului urinar, infecii la
nivelul urechii medii, n formarea plcii dentare, a gingivitei, pe suprafeele inerte ale dispozitivelor implantate
(catetere, valve cardiace protetice, implanturi dentare i dispozitive intrauterine).
n prezenta lucrare, autorii fac o aducere la zi asupra cunotinelor actuale privind aspectele teoretice ale
mecanismelor celulare care afecteaz fiziologia i patologia microbian, iar buna nelegere a proceselor din
biofilmul microbian ar trebui s conduc la strategii eficiente asupra controlului biofilmului i la mbuntirea
managementului pacientului.
Cuvinte cheie: biofilm microbian, formarea biofilmului, antibiorezisten, profilaxia infeciilor,
managementul pacientului
ABSTRACT
Microbial biofilm is an aggregate of microorganisms which can be formed on living or non-living surfaces and
can be spread everywhere in nature.
Common infectious processes involving biofilms include urinary tract infections, middle ear infections, dental
plaque, gingivitis, inert surfaces of implanted devices (catheters, prosthetic heart valves, dental implants and
intrauterine devices).
In this paper the authors have done an update of the current knowledge of the theoretical aspects of cellular
mechanisms that affect microbial physiology and pathology; hence a better understanding of the microbial
biofilm processes resulting in effective strategies of the control of biofilm and improvement of patient
management.
Key words: microbial biofilm, biofilm formation, antibiotic resistant bacteria, infection
prevention, patient management
INTRODUCERE
Biofilmul microbian este un agregat de microorganisme n care celulele ader mpreun pe o
suprafa, fiind ncorporate ntr-o matrice sintetizat
din substana polimeric extracelular (EPS). Biofilmele se pot forma pe suprafee vii sau non-vii, i
pot fi rspndite pretutindeni n natur (1,2). Micro-
Adres de coresponden:
Dr. Biol.Carmen Defta, Universitatea de Medicin i Farmacie Carol Davila, Str. Dionisie Lupu Nr. 37, Bucureti
e-mail: carmendefta@yahoo.co.uk
284
285
FORMAREA BIOFILMULUI
Mecanismul de formare a biofilmului microbian
(Fig. 1) se deruleaz pe parcursul a mai multor
etape (6).
Fixarea iniial: ncepe cu o ataare reversibil
de o suprafa a bacteriilor liber-plutitoare. Aceti
primi coloniti ader slab la suprafa, legndu-se
prin fore Van der Waals.
Ataarea ireversibil: dac colonitii nu sunt
ndeprtai imediat de pe suprafa, ei se pot ancora
mai ferm folosindu-se de structurile de adeziune
celular, cum sunt pilii.
Maturizarea I. Primii coloniti faciliteaz sosirea altor celule prin furnizarea diverselor situsuri
de adeziune, prin nceperea construciei matricei
care ine unit biofilmul. Cteva specii nu sunt capabile s se ataeze prin suprafeele lor, dar adesea
sunt capabile s se ancoreze la matrice sau direct la
primii coloniti. n timpul colonizrii aceste celule
sunt capabile s comunice prin molecule semnal
quorum sensing (Fig. 2) sau folosind produi ca
lactonele homoserin acilate (AHL).
Maturizarea a II-a. Odat iniiat colonizarea,
biofilmul crete prin combinaia dintre diviziunea
celular i recrutarea de noi celule. Etapa final a
formrii biofilmelor este cunoscut sub numele de
dezvoltare, reprezentnd stadiul n care biofilmul
este stabil i se poate modifica numai n form i
dimensiune. Dezvoltarea unei colonii de celule
agregate sub forma biofilmului poate permite s fie
din ce n ce mai rezistent la antibiotice.
Dispersia de celule din colonia biofilmului.
Aceasta etap permite biofilmelor s se rspndeasc i s colonizeze noi suprafee, constituind o etap
esenial a ciclului de via a biofilmelor. Enzimele
care degradeaz matricea extracelular a biofilmului
sunt dispersin B (DspB) i deoxyribonucleazele, cu
rol n dispersia acestora (7,8). Enzimele de degradare a matricii biofilmelor pot fi utilizate ca ageni
anti-biofilm (9,10). Dovezi recente au artat c un
mesager de acid gras, acidul cis-2-decenoic, este
capabil s determine inhibarea dispersiei i creterea
coloniilor biofilmului. S-a demonstrat, de asemenea,
c la concentraii subtoxice, oxidul de azot declaneaz dispersia biofilmelor (12,13). Oxidul nitric
poate fi potenial folosit pentru tratamentul pacienilor care sufer de infecii cronice care au la baz
biofilmele (14).
MATRICEA EXTRACELULAR
Biofilmul este susinut i protejat de o matrice
de compui polimerici sintetizai de componentele
proprii (EPS). EPS este o abreviere pentru toate
substanele extracelulare polimerizate sau exopolizaharide. Aceast matrice protejeaz celulele din
cadrul acestuia i faciliteaz comunicarea ntre ele
prin semnale biochimice. S-au gsit unele biofilme
care conin canale de ap, ce ajut distribuia de
substane nutritive i molecule de semnalizare.
Aceast matrice este suficient de puternic pentru
c, n anumite condiii, biofilmul poate deveni fosilizat.
Bacteriile care triesc ntr-un biofilm au de
obicei proprieti semnificativ diferite de bacteriile
liber-plutitoare din aceeai specie, protejate de mediul dens al biofilmului ce le permite s coopereze
i s interacioneze n moduri diferite. Un beneficiu
al acestui mediu este rezistena crescut la detergeni
i antibiotice, matricea dens extracelular i stratul
exterior de celule protejeaz interiorul comunitii.
n unele cazuri, rezistena la antibiotice poate fi
crescut de o mie de ori (15). Transferul lateral de
gene este mult facilitat n biofilme i conduce la o
structur mai stabil a acestora (16). Cu toate
acestea, biofilmele nu sunt ntotdeauna mai rezistente la antibiotice. Aceast rezisten la antibiotice,
n ambele faze de celule staionare i biofilm, poate
fi cauzat de prezena celulelor persister (17).
Biofilmele sunt omniprezente; aproape fiecare
specie de microorganisme are mecanismele prin
care acestea pot adera la suprafee i ntre ele. Biofilmele se pot forma pe aproape orice suprafa
imobil ntr-un mediu apos nesteril (sau foarte
umed).
Biofilmele sunt prezente pe dinii celor mai
multe animale, n formarea plcii dentare, caz n
care pot produce carii i boli gingivale. Biofilmele
au fost gsite a fi implicate ntr-o mare varietate de
infecii microbiene n organism, estimnd 80% din
totalul infeciilor (18).
Procesele infecioase comune n care au fost
implicate biofilme includ infeciile tractului urinar,
infecii de cateter, infecii la nivelul urechii medii,
n formarea plcii dentare, a gingivitei (19); cele
date de lentile de contact (20) sunt implicate mai
puin frecvent, n procese mult mai letale, cum ar fi
endocardita, infeciile din fibroza chistic i infecii
ale dispozitivelor permanente, cum sunt protezele
comune, valvele cardiace i implanturi dentare
(21,22,23). Mai recent, s-a constatat c biofilmele
bacteriene pot afecta vindecarea rnilor cutanate i
reduc eficiena n tratarea antibacterian a rnilor
infectate ale pielii (24) .
286
FIGURA 1. Mecanismul
de formare a biofilmului
microbian (dup Finkel,
J.S., Mitchell, A.P.
Nature Reviews
Microbiology, 2011, 9,
109-118)
287
288
289
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