Miguel Cacho Teixeira

Nuno Pereira Mira

PubMed

Nuno P. Mira

Miguel C. Teixeira

Frontiers - Publisher Connector

EDITORIAL
published: 30 December 2013
doi: 10.3389/fmicb.2013.00416
Microbial mechanisms of tolerance to weak acid stress
Nuno P. Mira* and Miguel C. Teixeira
Biological Sciences Research Group, Department of Bioengineering, Institute for Biotechnology and Bioengineering, Instituto Superior Técnico,
Universidade de Lisboa, Lisbon, Portugal
*Correspondence: nuno.mira@ist.utl.pt
Edited by:
Thomas E. Hanson, University of Delaware, USA
Keywords: carboxylic acids, weak acid food preservatives, response and resistance to weak acid stress, food-borne spoilage microbes, tolerance to weak
acids
Carboxylic acids are ubiquitous molecules found in microbial
metabolic pathways and that have been explored for a wide array
of applications including food preservation (e.g., acetic, propi-
onic, benzoic, and sorbic acids), chemotherapy (e.g., the analgesic
acetylsalicylic acid, the immunosuppressor mycophenolic acid or
the antimalarial drugs artesunic and artemisinic acids) or agri-
culture (e.g., the herbicides 2,4-dichlorophenoxyacetic acid). This
research topic contributes to the understanding of the molec-
ular mechanisms underlying adaptation to weak acid stress in
microbes [extensively reviewed in Piper et al. (2001); Boot et al.
(2002); Cotter and Hill (2003); Smits and Brul (2005); Mollapour
et al. (2008); Teixeira et al. (2011)], a knowledge base that impacts
the fields of Medicine, Health, Food Safety, and the Environment.
The exploitation of carboxylic acids as “building-block
molecules” for chemical synthesis has recently been a hot topic
of research, accompanying the orientation of US and EU pol-
icy towards the development of biorefineries(Sauer et al., 2008;
Abbott et al., 2009). To be economically sustainable biomass-
based refineries must efficiently produce biofuels, but must also
produce effective alternatives to the oil-derivatives that are used
today as precursors/catalysts by the chemical industry. The car-
boxylic group, along with other functional groups frequently
found in carboxylic acids, make these molecules attractive plat-
forms for chemical synthesis and/or catalysis. The efforts put
by the scientific community to develop efficient processes for
large-scale production of carboxylic acids from renewable carbon
sources, exploring different microbes as cell factories, have led to
significant improvements (Sauer et al., 2008; Abbott et al., 2009);
however, the yield of microbial carboxylic acid production is still
limited. This low yield is mainly caused by to the toxic effects of
the acids in the producing cells and by the diversion of substrate
towards metabolites other than the acid of interest. The article
of Jarboe et al. (2013) reviews the toxic effects exerted by, and
the underlying adaptive responses to, lipophilic carboxylic acids
in Saccharomyces cerevisiae and Escherichia coli, two host systems
that have been exploited as cell factories. Within the same con-
text, Steiger et al. (2013) review themost recent findings regarding
biosynthesis of itaconic acid in Aspergillus terreus as well as the
metabolic- and genetic engineering-based strategies attempted to
improve the yield of production of this acid in this fungus and in
other hosts.
The ability of microbial pathogens to colonize the human body
is frequently dependent on their ability to tolerate carboxylic
acids. This the case of probiotic bacteria that need to tolerate
the presence of bile salts (composed by bile acids conjugated
with glycine or taurine) to colonize the gut, or of Candida
species that need to cope with acetic and lactic acids in the vagi-
nal tract, produced by the bacteria that co-colonize that niche.
Ruiz et al. (2013) review the main adaptive responses of probi-
otic Lactobacilli and Bifidobacteria to cope with the toxic effect
exerted by bile salts and by bile. Several reports on adaptive
mechanisms to weak acids in Candida are featured as well. The
involvement of the multidrug (MDR) transporter of the Major
Facilitator Superfamily (MFS) CgAqr1 in C. glabrata tolerance to
acetic acid and to the antifungal drugs flucytosine and clotrima-
zole is herein demonstrated (Costa et al., 2013). The involvement
of the HOG1-signalling pathway, controlled by the Hog1 pro-
tein kinase, in C. glabrata tolerance and response to sorbic acid
is described by Jandric et al. (2013). Sorbic acid is widely used as
a preservative in over-the-counter vaginal products and therefore
the identification of genes/proteins involved in C. glabrata resis-
tance to this compound is detrimental to improve the efficacy of
those products and, consequently, to control infections caused by
this pathogenic yeast.
Weak carboxylic acids (e.g., acetic, propionic, sorbic and
benzoic acids) are important food preservatives and spoilage
microbes must overcome their presence to grow in food products.
Much of what is known today regarding the mechanisms under-
lying tolerance and resistance to weak acid food preservatives in
spoilage Fungi, particularly at a genome-wide scale, was gath-
ered in the experimental eukaryotic model yeast Saccharomyces
cerevisiae, itself a spoilage yeast (Piper et al., 2001; Mollapour
et al., 2008; Mira et al., 2010). Two studies dedicated to S. cere-
visae responses to weak acid stress are included in this research
topic. The review of Giannattasio et al. (2013) focuses on the
equilibrium between the activation of pro-survival or pro-death
mechanisms described to occur in acetic acid-stressed yeast cells.
The second study, undertaken by Ullah et al. (2013), shows that
under extreme weak acid stress S. cerevisiae cells prefer to preserve
energy reserves thus limiting the activation of energy-consuming
adaptive mechanisms (such as the activity of the plasma mem-
brane proton pump). Results from Ullah et al. also reinforce a
previous hypothesis that yeast cells adapt to weak acid stress by
modifying the cell envelope to reduce the diffusion rate of the
undissociated acid to the intracellular environment (Simoes et al.,
2006; Mira et al., 2009). The study of Diakogiannis et al. (2013)
shows that this mechanism of diffusional restriction is also rele-
vant for protection against weak acid toxicity in the food-borne
pathogen Listeria monocytogenes. The response of Campylobacter
jejuni, also a food-borne pathogen, to formic acid is the scope
www.frontiersin.org December 2013 | Volume 4 | Article 416 | 1
Mira and Teixeira Microbial tolerance to weak acids
of the study performed by Kassem et al. (2013). Formic acid has
been used as a feed additive to reduce emergence of C. jejuni in
chickens, the primary reservoir of this pathogen. However, the
data obtained suggest that formic acid might act as an inducer
(or at least a positive modulator) of entry of C. jejuni cells
into a viable-but-not-culturable (VBNC) state that allows these
bacterial cells to become untraceable. The development of a pH-
sensitive fluorescent probe to monitor the internal pH of Bacillus
subtillis cells is the goal of the study of Van Beilen and Brul (2013).
Using this newly developed probe the authors demonstrate that
germination of B. subtillis spores involves a prominent increase in
internal pH up to 7 (Van Beilen and Brul, 2013). In the presence
of inhibitory concentrations was not altered of sorbic acid in the
extracellular milieu reduced the germination rate and abrogated
the increase in internal pH, while no significant effect was regis-
tered under acetic acid stress (Van Beilen and Brul, 2013). It thus
seems that sorbic acid is more suited to prevent contamination of
food products with B. subtillis than acetic acid.
Altogether this research topic highlights the importance of
pursuing the in-depth study of the molecular mechanisms under-
lying the toxicity and resistance to weak organic acids as an
important way to contribute for the development of more
appropriate tools for the control and elimination of food-borne
pathogens/contaminants that thrive in acidic environments and
for the engineering of optimized strains to be used as superior
cell factories, able to tolerate inhibitory weak acid concentrations,
among other fermentation-related stresses.
ACKNOWLEDGMENTS
All the reviewers that actively participated in the peer-review of
the articles published within the scope of this research topic are
acknowledge for their valuable contributions.
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Received: 13 December 2013; accepted: 18 December 2013; published online: 30
December 2013.
Citation: Mira NP and Teixeira MC (2013) Microbial mechanisms of tolerance to
weak acid stress. Front. Microbiol. 4:416. doi: 10.3389/fmicb.2013.00416
This article was submitted to Microbial Physiology and Metabolism, a section of the
journal Frontiers in Microbiology.
Copyright © 2013 Mira and Teixeira. This is an open-access article distributed under
the terms of the Creative Commons Attribution License (CC BY). The use, distribu-
tion or reproduction in other forums is permitted, provided the original author(s)
or licensor are credited and that the original publication in this journal is cited, in
accordance with accepted academic practice. No use, distribution or reproduction is
permitted which does not comply with these terms.
Frontiers in Microbiology | Microbial Physiology and Metabolism December 2013 | Volume 4 | Article 416 | 2


Microbial mechanisms of tolerance to weak acid stress

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http://dx.doi.org/10.3389/fmicb.2013.00416

Microbial mechanisms of tolerance to weak acid stress

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