[ Pobierz całość w formacie PDF ]

terial cell wall responsible for the high biocide resistance are sensitive to, and were lysed by, these membrane-active agents.
currently unknown, although some information is available. Therefore, the cell wall in whole cells is responsible for their
Inhibitors of cell wall synthesis increase the susceptibility of modified response.
M. avium to drugs (391); inhibition of myocide C, arabinoga- In nature, S. aureus may exist as mucoid strains, with the
lactan, and mycolic acid biosynthesis enhances drug suscepti- cells surrounded by a slime layer. Nonmucoid strains are killed
bility. Treatment of this organism with m-fluoro-DL-phenylala- more rapidly than mucoid strains by chloroxylenol, cetrimide,
nine (m-FL-phe), which inhibits mycocide C synthesis, produces and chlorhexidine, but there is little difference in killing by
significant alterations in the outer cell wall layers (106). Eth- phenols or chlorinated phenols (263); removal of slime by
ambutol, an inhibitor of arabinogalactan (391, 501) and phos- washing rendered the cells sensitive. Therefore, the slime
pholipid (461, 462) synthesis, also disorganizes these layers. In plays a protective role, either as a physical barrier to disinfec-
addition, ethambutol induces the formation of ghosts without tant penetration or as a loose layer interacting with or absorb-
the dissolution of peptidoglycan (391). Methyl-4-(2-octadecyl- ing the biocide molecules.
cyclopropen-1-yl) butanoate (MOCB) is a structural analogue There is no evidence to date that vancomycin-resistant en-
of a key precursor in mycolic acid synthesis. Thus, the effects of terococci or enterococci with high-level resistance to amino-
MOCB on mycolic acid synthesis and m-FL-phe and etham- glycoside antibiotics are more resistant to disinfectants than
butol on outer wall biosynthetic processes leading to changes are antibiotic-sensitive enterococcal strains (9, 11, 48, 319).
in cell wall architecture appear to be responsible for increas- However, enterococci are generally less sensitive to biocides
ing the intracellular concentration of chemotherapeutic drugs. than are staphylococci, and differences in inhibitory and bac-
These findings support the concept of the cell wall acting as a tericidal concentrations have also been found among entero-
permeability barrier to these drugs (425). Fewer studies have coccal species (257).
been made of the mechanisms involved in the resistance of Intrinsic resistance of gram-negative bacteria. Gram-nega-
mycobacteria to antiseptics and disinfectants. However, the tive bacteria are generally more resistant to antiseptics and
activity of chlorhexidine and of a QAC, cetylpyridinium chlo- disinfectants than are nonsporulating, nonmycobacterial gram-
ride, against M. avium and M. tuberculosis can be potentiated in positive bacteria (Fig. 2) (428, 440, 441). Examples of MICs
the presence of ethambutol (52). From these data, it may be against gram-positive and -negative organisms are provided in
inferred that arabinogalactan is one cell wall component that Table 6. Based on these data, there is a marked difference in
acts as a permeability barrier to chlorhexidine and QACs. It is the sensitivity of S. aureus and E. coli to QACs (benzalkonium,
not possible, at present, to comment on other components, benzethonium, and cetrimide), hexachlorophene, diamidines,
since these have yet to be investigated. It would be useful to and triclosan but little difference in chlorhexidine susceptibil-
have information about the uptake into the cells of these an- ity. P. aeruginosa is considerably more resistant to most of
tiseptic agents in the presence and absence of different cell wall these agents, including chlorhexidine, and (not shown) Proteus
synthesis inhibitors. spp. possess an above-average resistance to cationic agents
One species of mycobacteria currently causing concern is such as chlorhexidine and QACs (311, 440).
M. chelonae, since these organisms are sometimes isolated from The outer membrane of gram-negative bacteria acts as a
endoscope washes and dialysis water. One such strain was not barrier that limits the entry of many chemically unrelated types
162 MCDONNELL AND RUSSELL CLIN. MICROBIOL. REV.
TABLE 7. Possible transport of some antiseptics and disinfectants into gram-negative bacteriaa
Antiseptic/disinfectant Passage across OMb Passage across IMb
Chlorhexidine Self-promoted uptake(?) IM is a major target site; damage to IM enables biocide to enter
cytosol, where further interaction occurs
QACs Self-promoted uptake(?); also, OM might present a IM is a major target site; damage to IM enables biocide to enter
barrier cytosol, where further interaction occurs
Phenolics Hydrophobic pathway (activity increases as hydro- IM is a major target site, but high phenolic concentrations coag-
phobicity of phenolic increases) ulate cytoplasmic constituents
a
Data from references 197, 433 to 435, 438, and 439.
b
OM, outer membrane; IM, inner membrane.
of antibacterial agents (18, 169, 196, 197, 355, 366, 440, 516, outer membrane LPS could be a contributing factor to this
517). This conclusion is based on the relative sensitivities of intrinsic resistance (97, 516).
staphylococci and gram-negative bacteria and also on studies A particularly troublesome member of the genus Providencia
with outer membrane mutants of E. coli, S. typhimurium, and is P. stuartii. Like Proteus spp., P. stuartii strains have been
P. aeruginosa (134, 135, 433 435, 438). Smooth, wild-type bac- isolated from urinary tract infections in paraplegic patients and
teria have a hydrophobic cell surface; by contrast, because of are resistant to different types of antiseptics and disinfectants
the phospholipid patches on the cell surface, deep rough (hep- including chlorhexidine and QACs (492, 496). Strains of P. stu-
tose-less) mutants are hydrophobic. These mutants tend to be artii that showed low-, intermediate-, and high-level resistance
hypersensitive to hydrophobic antibiotics and disinfectants. to chlorhexidine formed the basis of a series of studies of the
Low-molecular-weight (Mr ca. 600) hydrophilic molecules resistance mechanism(s) (86, 422, 428). Gross differences in
readily pass via the porins into gram-negative cells, but hydro- the composition of the outer layers of these strains were not
phobic molecules diffuse across the outer membrane bilayer detected, and it was concluded that (i) subtle changes in the
(Table 7). In wild-type gram-negative bacteria, intact LPS mol- structural arrangement of the cell envelopes of these strains
ecules prevent ready access of hydrophobic molecules to phos- was associated with this resistance and (ii) the inner membrane
pholipid and thence to the cell interior. In deep rough strains, was not implicated (230).
which lack the O-specific side chain and most of the core Few authors have considered peptidoglycan in gram-nega-
polysaccharide, the phospholipid patches at the cell surface tive bacteria as being a potential barrier to the entry of inhib-
have their head groups oriented toward the exterior. itory substances. The peptidoglycan content of these organisms
In addition to these hydrophilic and hydrophobic entry path- is much lower than in staphylococci, which are inherently more [ Pobierz całość w formacie PDF ]