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Quaternary ammonium disinfectants: microbial
adaptation, degradation and ecology
Ulas Tezel1 and Spyros G Pavlostathis2
Disinfectants play an important role in maintaining acceptable
health standards by significantly reducing microbial loads as
well as reducing, if not eliminating, pathogens. This review
focuses on quaternary ammonium compounds (QACs), a
widely used class of organic disinfectants. Specifically, it
reviews the occurrence, microbial adaptation, and degradation
of QACs, focusing on recent reports on the ecology of QACdegraders, the pathways and mechanisms of microbial
adaptation which lead to resistance to QACs, as well as to
antibiotics. With the help of culture-dependent and nonculturedependent tools, as well as advanced analytical techniques, a
better understanding of the fate and effect of QACs and their
biotransformation products is emerging. Understanding the
underlying mechanisms and conditions that result in QAC
resistance and biodegradation will be instrumental in the
prudent use of existing QAC formulations and foster the
development of safer disinfectants. Development and
implementation of (bio)technologies for the elimination of QACs
from treated wastewater effluents will lessen adverse impacts
to both humans and the environment.
Addresses
1
The Institute of Environmental Sciences, Bogazici University, Bebek,
Istanbul 34342, Turkey
2
School of Civil and Environmental Engineering, Georgia Institute of
Technology, Atlanta, GA 30332-0512, USA
Corresponding author: Pavlostathis, Spyros G
([email protected])
Current Opinion in Biotechnology 2015, 33:296–304
This review comes from a themed issue on Environmental
biotechnology
Edited by Spiros N Agathos and Nico Boon
sub-inhibitory) concentrations of biocides. Recent studies
suggest that exposure to sub-inhibitory biocide concentrations facilitates the evolution of resistance to the
biocide, and may also lead to co-resistance and crossresistance to other antimicrobial agents such as antibiotics
[1,2].
Quaternary ammonium compounds (QACs) are cationic
surfactants introduced in the late 1930s along with the
first antibiotics, sulfonamides. They are classified as ‘high
production volume’ chemicals [3]. The chemical structure of QACs depends on the four aliphatic or aromatic
moieties attached to the central nitrogen atom
(R1R2N+R3R4). QACs are mainly used in disinfectant
and antiseptic formulations utilized in homes, human
and animal healthcare facilities, agriculture and industry.
They are effective against a variety of bacteria, fungi and
viruses at very low concentrations. When QACs are used
as disinfectants, the applied concentration is typically
between 400 and 500 ppm and almost always below
1000 ppm (e.g., 0.1% w/v in Lysol1) [3]. Domestic,
hospital and industrial use of QACs results in QACsbearing waste/wastewater. Because typical wastewater
treatment plants are designed to remove major, easily
degradable organics, most trace contaminants, including
QACs, pass through wastewater treatment plants and are
released into the environment. About 75% of QACs
utilized annually are released into wastewater treatment
systems, whereas the rest are discharged directly into the
environment. The mean concentration of QACs in domestic wastewater, treated effluent wastewater, sewage
sludge and surface water is reported to be around 0.5 mg/
L, 0.05 mg/L, 5000 mg/kg dry weight, and 0.04 mg/L,
respectively, which is significantly below applied concentrations [3–5].
http://dx.doi.org/10.1016/j.copbio.2015.03.018
0958-1669/# 2015 Elsevier Ltd. All rights reserved.
Introduction
Disinfectants are extensively used and their formulations
contain active ingredients at levels well above the minimum inhibitory concentration (MIC) of targeted microorganisms. Inappropriate application of disinfectants,
dilution in the environment after discharge and biodegradation result in biocide concentration gradients. Thus,
microorganisms are frequently exposed to non-lethal (i.e.,
Current Opinion in Biotechnology 2015, 33:296–304
Because QACs are biodegradable under aerobic conditions, their concentrations in indoor and outdoor environments continuously fluctuate. As a result, microorganisms
are exposed to QACs dynamically over a wide range of
concentrations (i.e., non-inhibitory, sub-inhibitory, overinhibitory concentrations). In general, environmental
concentrations of QACs are well below the MIC values.
Sewage, biological wastewater treatment units, surface
waters and sediments are environments where QACs are
present at sub-inhibitory concentrations. When the high
microbial diversity in these environments is coupled to
sub-inhibitory QAC concentrations, such environments
become selective, resulting in the emergence and dissemination of QAC resistance among different bacterial
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Quaternary ammonium disinfectants Tezel and Pavlostathis 297
genera, which may also include clinically important
pathogens. Because many of the QAC resistance pathways and mechanisms are similar to those involved in
antibiotic resistance, understanding QAC resistance and
dissemination is very important in the context of the
global antibiotic resistance problem. Although some suggest that there is no clear relationship between antibiotic
resistance and exposure of microorganisms to QACs [6],
many studies have shown that, for instance, exposure to
QACs results in dissemination of integrons (i.e., promoterless mobile recombinational elements) which harbor
resistance genes [7,8]. Evidence that soil bacteria and
human pathogens share similar resistomes within integrons [9] suggests that there is a link between antibiotic
resistance in nature and clinical settings, which is favored
by exposure to QACs.
Many reviews exist on the fate and effect of QACs in the
environment, QAC-related antimicrobial resistance, and
implications of QAC resistance to human health [3,10,11].
In this review, we discuss the ecology of QACs-exposed
microbial communities, as well as the pathways and
mechanisms of microbial adaptation to sub-inhibitory
QAC concentrations following the context of a recent
review by Andersson and Huges by linking the similarities of antibiotic and disinfectant resistance [12]. In
addition, we consider the role of QAC biodegradation
on the evolution and dissemination of QAC resistance by
creating microenvironments with sub-inhibitory QAC
concentrations. Moreover, technologies utilizing novel
QAC-degraders for the alleviation of QAC contamination
are discussed.
Pathways and mechanisms of QAC resistance
at sub-inhibitory concentrations
The mode of action of QACs above MIC in bacteria is
disruption of the cell membrane’s physical and ionic
stability [13]. For example, benzalkonium chlorides
(BACs) bind to the cell membrane of Pseudomonas fluorescens by ionic and hydrophobic interactions, bringing
about changes of membrane properties and function,
followed by cellular disruption, loss of membrane integrity, ultimately resulting in leakage of essential intracellular constituents [14,15]. Above MIC, bacteria with
durable cell membrane are selected and proliferate. On
the other hand, the mode of action of QACs at sub-MICs
is complicated and always includes multiple processes
such as loss of membrane osmoregulation, inhibition of
respiratory enzymes, the dissipation of proton motive
force and oxidative stress, which triggers SOS response,
inducing error-prone DNA replication leading to mutations and gene transfers [16,17]. Adaptation to QACs at
sub-MICs is achieved by modification of the outer membrane, cell membrane, density and structure of porins,
regulatory hyperexpression of efflux pumps, and acquisition of QAC-specific efflux pumps through mobile recombinational elements, such as plasmids and integrons
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upon oxidative stress or (followed by) stress-induced
mutagenesis [3].
Major pathways in the evolution of resistance at subinhibitory antibiotic concentrations have been recently
reviewed [12,18]. Bacteria follow similar pathways while
adapting to QACs. Exposure to QACs at sub-MIC creates
(oxidative) stress. For instance, exposure of E. coli to
cetyltrimethylammonium bromide resulted in intracellular production of superoxide and hydrogen peroxide [19].
Bacteria compensate for oxidative stress by SOS-response
and induction of stress-response sigma factors rpoS, promoting cell survival by DNA repair, while nucleotide
polymorphism may occur, resulting in mutations. Oxidative stress responses also boost gene transfer and recombination events via prophages, transposons, integrons and
integrative-conjugative elements (ICE) (Figure 1). As a
result, resistant sub-populations evolve and dominate in a
microbial community upon exposure to any antimicrobial
agent [20]. Major mechanisms of adaptation to QACs
include modification of cell membrane structure and
composition, enhanced biofilm formation, acquisition of
efflux genes, overexpression of efflux pump systems, and
biodegradation. Generally, multiple mechanisms co-develop during adaptation of bacteria to QACs [21].
Exposure to QACs at sub-MICs enhances biofilm formation [22]. QAC resistant strains of bacteria form biofilms
faster and these species are less susceptible to QACs than
planktonic species [23]. Presence of multiple species in
biofilms increases QAC resistance [24,25]. Expression
of certain genes enhanced biofilm formation by QAC
resistant Listeria monocytogenes [26,27].
Several mutations result in selection of bacteria with
reduced cell permeability. Resistant cells have modified
cell membrane fatty acids, phospholipids, and outer
membrane lipopolysaccharides [28], resulting in a more
anionic and hydrophobic cell surface, thus restricting easy
passage of the QACs through the cell surface. Other cell
modifications in response to exposure to QACs are density reduction and composition change of the porins
[29,30], as well as change of the outer membrane protein
composition [31].
Efflux-mediated QAC resistance has received significant
interest because it has a genetic origin, confers co-resistance to antibiotics and is transferable among species
through horizontal gene transfer. Multidrug efflux pumps
mediate the transfer of biocides from the inside to the
outside of the cell through an energy or proton-dependent
mechanism. Efflux determinants, which confer resistance
to QACs, are given in Table 1. QAC resistance via efflux
pumps follows two mechanisms. First, QAC resistance is
induced by overexpression of efflux pumps upon exposure to QAC or as a result of QAC-induced stress. Such
stress either triggers a regulatory system that controls the
Current Opinion in Biotechnology 2015, 33:296–304
298 Environmental biotechnology
Figure 1
Acquisition of efflux genes
Gene
cassettes
Integron
recombination
tI
E
cΔ
In
qa
lI
Su
HGT and recombination
ICE induction
Biodegradation
Enhanced biofilm formation
Transposition
RpoS induction
Cl –
N+
G
TT
Error-prone
replication
Error-prone
DNA polymerase
sRNA
Inhibition of
mismatch repair
A
TT
Modification of cell membrane
Mutations
Sub-MIC
QAC concentration
SOS response
Prophage induction
Over-expression of efflux
Replicative
DNA polymerase
Current Opinion in Biotechnology
Pathways and mechanisms of QAC resistance (adapted from Ref. [12]).
expression of an efflux determinant or causes a mutation
resulting in the overexpression of the efflux determinant
or increase in its extrusion efficiency [32]. These efflux
pumps are generally chromosomally encoded and act
against a wide array of antimicrobial agents. Overexpression of these efflux pumps results in a two-fold to eightfold increased tolerance of the adapted bacteria to QACs
and other substrates of these pumps [1,33–36]. For
instance, the study by Mc Cay et al. [1] showed that
Pseudomonas aeruginosa, variants of which are pathogenic,
grown in continuous culture at subinhibitory concentrations of BAC resulted in increased resistance to both BAC
and ciprofloxacin; its antibiotic resistance was attributed
to amino acid substitution (Val-51AAla) in nfxB, the Mex
efflux system regulator gene.
The second mechanism of QAC resistance is through
acquisition of genes for specialized QAC efflux pumps,
Table 1
Efflux determinants conferring QAC resistance (adapted from Ref. [61])
Efflux family
Efflux proteins extruding QACs
Typical antibiotic substrates
Resistance nodulation
division (RND)
YhiUV-TolC, AcrAB-TolC, MexAB-OprM, CmeABC,
CmeDEF, SdeXY, OqxAB
Major facilitator
superfamily (MFS)
QacA, QacB, NorA, NorB, MdeA, EmeA, MdfA
Multidrug and toxic
compound extrusion (MATE)
MepA, NorM, PmpM
Aminoglycosides, b-lactams, Chloramphenicol,
Erythromycin, Fluoroquinolones, Novobiocin,
Rifampin, Tetracyclines, Trimethoprim
Aminoglycosides, Chloramphenicol,
Erythromycin, Fluoroquinolones, Lincosamides,
Novobiocin, Rifampin, Tetracyclines
Aminoglycosides, Fluoroquinolones
Small multidrug resistance (SMR)
QacE, QacED1, QacF, QacG, QacH, QacI, QacJ,
smr, EmrE, SugE
Aminoglycosides, Chloramphenicol,
Erythromycin, Tetracyclines
Current Opinion in Biotechnology 2015, 33:296–304
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Quaternary ammonium disinfectants Tezel and Pavlostathis 299
which belong to the SMR family. Among them, EmrE,
smr and SugE are multidrug efflux pumps [37], whereas
QacE, QacDE, QacF, QacG, QacH, QacI, QacJ and QacZ
are QAC-specific efflux determinants [38]. The genes of
these efflux proteins are mainly found in mobile genetic
elements such as transposons, ICEs, plasmids and integrons. As a result, they can be horizontally transferred
between bacteria of the same or different genera. Such
genes are abundant in the environment.
Acquisition of QAC efflux genes by bacteria involves
integration of genes to integrons and plasmids or recombination of efflux gene containing ICE and transposons
into the recipient genome. Oxidative stress response
plays a crucial role in both QAC resistance mechanisms.
Integrons play a significant role in the acquisition and
mobilization of QAC resistance genes [39]; they are found
in many environmental bacterial species, particularly in
those exposed to QACs and/or antibiotic residues [40,41].
QAC contamination is also responsible for the stabilization of integrons and their gene cassettes [42]. A direct
link between SOS response and the expression of integron integrases was demonstrated. SOS regulation
enhances cassette swapping and capture under stressful
conditions, such as during QAC exposure [43].
Plasmids also play a significant role in harboring and
disseminating genes related to resistance to QACs and
other biocides. Plasmids of the incompatibility (Inc)
group IncP-1, also called IncP, as extrachromosomal
genetic elements can be transferred and replicated virtually in all Gram-negative bacteria. IncP-1group plasmids
are broadly distributed in environments with sub-inhibitory QAC concentrations, such as soils and wastewater
treatment plants. IncP plasmids commonly harbor QAC
resistance genes along with many other resistance genes
[44–47]. In addition, plasmid-associated QAC resistance
genes were transferred between non-pathogenic and
pathogenic bacteria exposed to QACs, a process that also
leads to the co-selection of resistance to other contaminants [48].
Using the SOS-response, ICEs are transferred from one
bacterial chromosome to another. ICEs containing multiple QAC resistance genes were identified in strains of
Vibrio scophthalmi, V. splendidus, V. alginolyticus, Shewanella
haliotis, and Enterovibrio nigricans isolated from fish grown
in marine aquaculture systems [49]. Exposure to biocides
below inhibitory concentrations also facilitates the conjugation of transposons [50]. Novel transposons carrying
QAC resistance genes have been identified in both Gramnegative and positive bacteria [51,52].
QAC biodegradation: ecology, mechanism
and genetics
Exposure of a microbial community to QACs results in
the development of resistance, as well as selection and
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proliferation of resistant bacteria. A very recent study
showed that when a microbial community, fed with an
organic carbon source was exposed continuously to QACs,
its diversity decreased substantially and was dominated
by Proteobacteria, mainly composed of Pseudomonads. In
addition, a versatile repertoire of antimicrobial resistance
genes, such as efflux pumps (e.g., RND family and SMR
family) and cell envelope modification systems (e.g.,
aminoarabinose lipid A modification) were amplified during a long-term exposure to BACs [53,54].
Aerobic biodegradation of QACs has been attributed
mainly to bacterial species in the genera of Xanthomonas,
Aeromonas, and Pseudomonas [3]. More recently, several
bacteria have been identified that are capable of QAC
degradation, such as Pseudomonas putida A ATCC
12633 [55], Pseudomonas nitroreducens B and DB [56],
Pseudomonas sp. BIOMIG1 (Ertekin and Tezel, 114th
General Meeting of American Society for Microbiology,
Abstract no: Q352) and Stenotrophomonas sp. B27 (unpublished). In addition, non-culture-based techniques, such
as cloning, metagenomics and pyrosequencing have been
used to elucidate the composition of QAC degrading,
enriched microbial communities. A microbial community
originating from a river sediment, utilizing BACs as the
sole carbon and energy source had a dramatically decreased phylogenetic diversity as compared to the control
(without BAC exposure), and was dominated by Pseudomonas species (>50% of the total) [53,54,57]. Metagenomic analysis revealed that community adaptation to
BACs occurred primarily via selective enrichment of
BAC-degrading Pseudomonas species, particularly P.
nitroreducens, and secondarily via amino acid substitutions
and horizontal transfer of selected genes, including a gene
encoding a PAS/PAC sensor protein and ring-hydroxylating dioxygenase genes [54,56]. In addition, multi-drug
efflux pump genes such as sugE, PmpM, mexAB-oprM
and mexEF-oprN were enriched in the BAC-degrading
community [53].
Based on the phylogenetic tree prepared using the 16S
rDNA sequences of QAC degrading isolates and predominant species in QAC degrading microbial communities,
Pseudomonas spp., particularly the P. putida and P. aeruginosa group, are key species in QAC degradation
(Figure 2a). In addition Stenetrophomonas spp. (g-Proteobacteria), and Achromobacter spp. (a-Proteobacteria) are
frequently identified in communities degrading QACs,
indicating that they play a role in the biodegradation of
QACs [54].
Three aerobic QAC biotransformation pathways, which
differ in the location of the initial reaction, have been
observed (Figure 3): (a) hydroxylation of the terminal C
of the alkyl chain (v-hydroxylation), followed by multiple
b-oxidation cycles, progressing toward the hydrophilic
moiety; (b) hydroxylation of the C adjacent to the central
Current Opinion in Biotechnology 2015, 33:296–304
300 Environmental biotechnology
Figure 2
(a)
(b)
P. fluorescens [D84013]
P. orientalis [AF064457]
47
P. aureofaciens [D84008]
67
100
P. chlororaphis [D84011]
100 P. caricapapayae [D84010]
84
P. syringae [D84026]
P. sp. 7–6 [AB278070]
87
P. putida [D84020]
86
86
P. putida ATCC 12633 [AF094736]
P. oryzihabitans [D84004]
48
P. putida strain B2
100
98
clone BAC5 [HE650699]
P. sp BIOMIG1
91
39 P. nitroreducens B [KC415111]
50 P. nitroreducens BD [KC415112]
97
clone BAC54 [HE650698]
74
P. nitroreducens strain B1
98
P. nitroreducens [D84021]
100 79
P. citronellolis [AB021396]
74
P. aeruginosa [Z76651]
P. balearica [U26418]
89
P. stutzeri [U26262]
P. denitrificans [AB021419]
100
P. pertucinogena [AB021380]
Stenotrophomonas sp. strain B27
52
100
BIOMIG OTU 7
93
Stenotrophomonas maltophilia [JN656280]
BIOMIG OTU 1
100
Achromobacter sp. LMG 3458 [HG324053]
E. coli K–12 [NR_102804]
Pseudomonas putida S16 AOx [YP_004703499]
100
100
0.06
100
Pseudomonas sp. HZN6 POAOx [AFD54463]
97
64
100
Pseudomonas nitroreducens strain B AOx [KJ911918]
Pseudomonas sp. HZN6 NAOx [AGH68979]
Arthrobacter sp. PAO19 AOx [WP_022875508]
90
Pseudomonas putida BIRD-1 AOx (E4RE15_PSEPB]
100
Pseudomonas putida BIRD-1 AOx (E4R7Q2_PSEPB]
Pseudomonas putida ATCC 12633 TTABMO [AFA52008]
0.6
Current Opinion in Biotechnology
Phylogenetic classification of: (a) QAC-degrading bacterial isolates (in red) and nucleotide sequences of species present in QAC-degrading
communities identified in community clone libraries based on 16S rDNA or by pyrosequencing (in blue); (b) QAC dealkylating genes (in red).
N (a-hydroxylation), followed by central fission, resulting in the separation of the hydrophobic from the hydrophilic moiety; and (c) hydroxylation of the methyl-C
attached to the central N, followed by fission of the
methyl group [3]. In spite of the fact that QACs have a
relatively high adsorption capacity resulting in their
transfer to anoxic/anaerobic environments, such as anaerobic digesters and aquatic sediments, limited information exists relatively to the fate of QACs under such
conditions. The transformation of BACs under anoxic,
nitrate reducing conditions was recently reported to be
initiated by means of an abiotic nitrite nucleophilic
substitution reaction (modified Hofmann reaction) producing alkyl dimethyl amines (tertiary amines) [3,58].
Under anaerobic conditions, there is no evidence of
mineralization of QACs that contain alkyl or benzyl
groups [3].
In spite of the fact that the energetic burden of the abovediscussed QAC biotransformation pathways (initial reaction) is the same, pathway-b starting with the cleavage of
the Calkyl–N bond is the most predominant. Although,
pathway-a was the first identified QAC biotransformation
pathway, it could not be demonstrated in later studies for
Current Opinion in Biotechnology 2015, 33:296–304
similar QACs. Moreover, the product of pathway-b, a
tertiary amine, is less toxic than the products of pathway-a and pathway-c [57]. The combination of these two
observations suggests that pathway-b is naturally selected
as a mechanism for QAC biotransformation to cope with
the toxic effects of QACs and to eliminate the detrimental
consequences of the other biotransformation pathways.
As a result, QAC biotransformation may have evolved as a
QAC-resistance mechanism.
None of the isolates described above, except Pseudomonas
sp. BIOMIG1, was able to grow on the non-alkyl containing amines, such as trimethyl amine and dimethyl amine,
after dealkylation. Activation of the C–H bond in the
QAC alkyl group was thought to commence with NADHdependent hydroxylation by a monooxygenase in the
presence of oxygen [3]. Recently, two enzymes responsible for QAC dealkylation have been identified. Tetradecyl trimethyl ammonium bromide monooxygenase
(TTABMO) identified in P. putida ATCC 12633 is a
typical flavoprotein that utilizes NADPH and FAD as
cofactor [55]. On the other hand, the enzyme responsible
for dealkylating BACs by Pseudomonas nitroreducens was
identified as a FAD-using amine oxidase (AOx-BAC)
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Quaternary ammonium disinfectants Tezel and Pavlostathis 301
Figure 3
R
X–
N+
X–
N+
R
O2
R
n-3
NADH 2
O
n-3
NAD
NADH 2
+ 2 H 2O
+
HO
HO
O2
X–
N+
OH
n-5
NAD
(a) ω-hydroxylation of terminal C of alkyl group
R
X–
N+
R
O2
n-3
NADH 2
X–
N+
n-3
NAD
O2
OH
NADH 2
R
X–
N
H+
O
+
+
n-3
2 H 2O
OH
NAD
(b) α-hydroxylation of C adjacent to N of alkyl group
O2
R
n-3
HO
X–
N+
R
NADH 2
NAD
X–
N+
n-3
O2
R
NADH 2
NAD
H + X–
N
+ HO
O
+ 2 H 2O
n-3
(c) α-hydroxylation of C of methyl group
Current Opinion in Biotechnology
Aerobic QAC biotransformation pathways.
[56]. AOx-BAC is phylogenetically more closely related
to P. putida amine oxidase and Pseudomonas sp. pseudooxynicotine amine oxidase than TTABMO (Figure 2b),
which suggests that there may be multiple enzymes
responsible for the initial steps in QAC biotransformation.
With the exception of certain dimeric gemini QACs,
almost all QACs are biodegradable under aerobic conditions [59]. QAC degraders play an important role in
mitigating QAC contamination in the environment. However, proliferation of QAC degraders and their transfer in
indoor environments are not desired because it would
decrease their antimicrobial efficacy, resulting in public
health problems. Efforts should be devoted to develop
technologies based on immobilized QAC degraders or
their enzymes for the treatment of QAC-bearing wastewater. For instance, P. putida ATCC 12633 immobilized
using alginate entrapment was able to remove 80% of
QACs within 48 hours at a concentration range between
35 and 315 mg/L [60]. To this end, QAC degraders have
to be physiologically and metabolically well characterized
and factors affecting QAC biodegradation identified. In
case QAC detoxifying enzymes are used, strategies to
enhance enzyme functionality by optimizing cofactor
requirements using directed enzyme evolution
approaches will need to be evaluated.
Conclusion and outlook
QACs are effective disinfectants that have contributed to
maintaining acceptable health standards by ensuring a
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significantly reduced microbial load, and thus the likelihood that pathogenic bacteria are also reduced, if not
eliminated. Because QACs are extensively used in domestic, agricultural, industrial and clinical applications,
humans and microorganisms are in constant contact with
them. Misuse, environmental dilution and biodegradation of QACs often create environments with low QAC
concentrations. At sub-inhibitory QAC concentrations,
QAC resistance emerges mainly as a bacterial response
to QAC-induced oxidative stress, often causing mutations
or facilitating gene transfer, ultimately leading to evolution and selection of QAC-resistant bacteria.
Wastewater, wastewater treatment plants, wastewater
sludge, sludge applied soil, surface waters, and aquatic
sediments are environments where QAC resistance
evolves and proliferates. QAC resistant bacteria may be
transferred from outdoor environments to indoors such as
homes and healthcare facilities. QAC resistance genes,
especially efflux genes, are frequently found in bacterial
isolates obtained from human/animal healthcare facilities.
These genes either confer resistance to multiple biocides
and antibiotics (co-resistance) or mobile genetic elements
that they are attached to carry resistance genes to other
biocides and antibiotics. Therefore, QAC resistant bacteria, if they are pathogenic, may pose a serious threat to
human health. In addition, QAC resistant bacteria may
decrease the efficacy of QAC disinfectants by creating
microenvironments habitable by QAC susceptible bacteria, as for example in the case of biofilms. Moreover,
Current Opinion in Biotechnology 2015, 33:296–304
302 Environmental biotechnology
QAC-degrading bacteria create QAC gradients in which
susceptible species survive or even develop QAC resistance and proliferate.
The connection between QAC degradation and resistance is not well understood. Is QAC degradation a
blessing or a curse? Given that QACs degrade, at least
under aerobic conditions, QACs could be considered as
relatively low risk disinfectants. However, QAC biodegradation creates sub-inhibitory concentrations where otherwise susceptible species may develop QAC resistance
through various pathways and mechanisms as described
above. Many species are phylogenetically closely related
to QAC-degraders. Upon chronic exposure to QACs,
these species could become resistant, but unfortunately
some of them are pathogenic (e.g., P. aeruginosa) [1,30].
If efficient QAC degraders are used in treatment technologies and then integrated into wastewater treatment
plants, release of QACs into the environment may be
avoided or at least minimized. As a result, QAC resistance
and QAC-induced antibiotic resistance might be reduced.
In conclusion, QACs are widely used in many disinfectant
formulations and will continue to be used in the future.
The underlying mechanisms and conditions that result in
QAC resistance and biodegradation, especially in the
environment, must be better understood for the prudent
use of existing QAC formulations, as well as the development of safer disinfectants. Development and implementation of (bio)technologies for the elimination of
QACs from treated wastewater effluents, along with many
emerging microcontaminants, will greatly reduce adverse
impacts to both humans and the environment.
Acknowledgements
U. Tezel acknowledges the EU Research Executive Agency and the
Scientific and Technological Research Council of Turkey (TUBITAK) for
funding QAC related research through project no. PCIG09-GA-2011-293665
and 113Y528, respectively. S.G. Pavlostathis was supported for research
related to this work by the U.S. National Science Foundation under Grant
CBET 0967130.
References and recommended reading
Papers of particular interest, published within the period of review,
have been highlighted as:
of special interest
of outstanding interest
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