Functionalized Nanomaterials for the Management of Microbial Infection. A Strategy to Address Microbial Drug Resistance. A volume in Micro and Nano Technologies

328 Pages·2016·19.17 MB·English

by  Rabah Boukherroub

Functionalized Nanomaterials
for the Management
of Microbial Infection
Functionalized Nanomaterials
for the Management
of Microbial Infection
A Strategy to Address Microbial Drug Resistance
Edited by
Rabah Boukherroub
CNRS, Lille University of Science and Technology,
Villeneuve d’Ascq, France
Sabine Szunerits
Lille University of Science and Technology,
Villeneuve d’Ascq, France
Djamel Drider
Lille University of Science and Technology,
Villeneuve d’Ascq, France
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List of Contributors
A. Alvarez-Ordóñez
University of León, León, Spain
P.C. Balaure
University Politehnica of Bucharest, Bucharest, Romania
Y. Belguesmia
Lille University of Science and Technology, Villeneuve d’Ascq, France
R. Boukherroub
CNRS, Lille University of Science and Technology, Villeneuve d’Ascq, France
K. Braeckmans
Ghent University, Ghent, Belgium; Centre for Nano- and Biophotonics, Ghent, Belgium
T. Coenye
Ghent University, Ghent, Belgium
L.M.T. Dicks
Stellenbosch University, Stellenbosch, South Africa
D. Drider
Lille University of Science and Technology, Villeneuve d’Ascq, France
A. Friedman
George Washington School of Medicine and Health Sciences, Washington, DC,
United States
D. Gudovan
University Politehnica of Bucharest, Bucharest, Romania
I. Gudovan
University Politehnica of Bucharest, Bucharest, Romania
I. Kempf
Unité Mycoplasmologie-Bactériologie, Ploufragan, France
B. Klumperman
Stellenbosch University, Stellenbosch, South Africa
B. Mordorski
Albert Einstein College of Medicine, Bronx, NY, United States
K. Naghmouchi
Université de Tunis El Manar, Tunis, Tunisia
L. Ruiz
Complutense University of Madrid, Madrid, Spain
S.K. Samal
Ghent University, Ghent, Belgium; Centre for Nano- and Biophotonics, Ghent, Belgium
ix
x List of Contributors
N. Škalko-Basnet
Drug Transport and Delivery Research Group, Department of Pharmacy,
Faculty of Health Sciences, University of Tromsø The Arctic University
of Norway, Tromsø, Norway
S. Szunerits
Lille University of Science and Technology, Villeneuve d’Ascq, France
E. Teirlinck
Ghent University, Ghent, Belgium; Centre for Nano- and Biophotonics, Ghent, Belgium
N. Tison
Lille University of Science and Technology, Villeneuve d’Ascq, France; Haute École
Louvain en Hainaut, HELHa, Mons, Belgium
A.D.P. van Staden
Stellenbosch University, Stellenbosch, South Africa
Ž. Vanić
Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry,
University of Zagreb, Zagreb, A Kovačića 1, Zagreb, Croatia
Preface
Bacteria usually must adhere to a cellular surface in order to cause disease. In some settings,
the adherent microbe physically invades the cellular layer and gains access to inner milieu,
as Salmonella or Shigella would in the intestine. In other scenarios, such as the airway of an
individual with cystic fibrosis, adherent Pseudomonas aeruginosa establishes a colony (a “bio-
film”) on the surface of the bronchial epithelium that resists antimicrobial therapy. Its presence
provokes a chronic inflammatory process that gradually destroys the airway. Similarly, infec-
tions of the urinary tract usually occur when a strain of Escherichia coli attaches to the surface
of the bladder, increases in number, and migrates upwards toward the kidneys. Furthermore,
the surfaces of medical devices that come into contact with bacteria generally become colo-
nized, be they catheters that are placed in a vein or artery, the urinary tract, or the airway.
Bacteria seem to love to grow on surfaces.
To treat bacterial infections we almost universally administer antibiotics, which are physically
quite small, relative to the size of the microbe. The antibiotic we introduce swarms around the
bacterial cell. If the concentration of the antibiotic in the blood, or in the urinary tract, or on
the surface of the airway is high enough, sufficient numbers of antibiotic molecules will pen-
etrate the bacterial cell and disable it, the sooner the better.
In this volume, Functionalized Nanomaterials for the Management of Microbial Infection,
Drs. Boukherroub, Szunerits, and Drider suggest that we ought to consider exploiting the pre-
dilection that microbes have for surfaces in our design of antibiotic therapeutics. The basic
idea is to use nanoparticles, which present a small but discrete surface that can physically con-
tact the bacterial cell. If the surface properties of the nanoparticle are optimal for the pur-
pose intended, the particle and bacterial cell will adhere to one another. If the nanoparticle is
decorated with antibiotics that can act despite being tethered to a surface, then the bacterial
cell will find itself facing a wall of deadly agents. (Antimicrobial peptides, including many of
the bacteriocins described in this volume, can inflict damage on the bacterial membrane and/
or proteoglycan wall, even when covalently bound to a surface). We learn in this volume that
lipids, various polymers, and even graphene, can be exploited as the nanoparticle carrier.
The development of nanoparticle antibiotics is very exciting. We all await the outcome of their
safety and efficacy in appropriate clinical trials.
M. Zasloff
Georgetown University Hospital, Washington, DC, United States
xi
1
Chapter
Resistance to Antibiotics and
Antimicrobial Peptides: A Need of Novel
Technology to Tackle This Phenomenon
Y. Belguesmia1, I. Kempf2, N. Tison1,3, K. Naghmouchi4 and D. Drider1
1Lille University of Science and Technology, Villeneuve d’Ascq, France 2Unité Mycoplasmologie-Bactériologie, Ploufragan,
France 3Haute École Louvain en Hainaut, HELHa, Mons, Belgium 4Université de Tunis El Manar, Tunis, Tunisia
CHAPTER OUTLINE
1.1 Resistance to Antibiotics 1
1.2 Resistance to Bacteriocins Produced by Gram-Positive Bacteria (GPB) 8
1.3 Conclusion and Prospects 14
Acknowledgements 15
References 15
1.1 RESISTANCE TO ANTIBIOTICS
Antimicrobials used for human or animal health include many different
families, such as β-lactams, aminoglycosides, macrolides, tetracyclines,
and polypeptides, which differ according to their chemical structures,
mechanisms of action, and spectra. Antibiotics are drugs of natural, syn-
thetic, or semi-synthetic origin that have, at low concentrations, the capac-
ity to kill or to inhibit the growth of bacteria whilst causing little or no
damage to the host. They can target the bacterial cell wall (β-lactam anti-
biotics, vancomycin, and bacitracin), the protein synthesis (macrolides,
aminoglycosides, tetracyclines, and chloramphenicol), affect nucleic acid
function (quinolones, rifampicin, and nitrofurans), or acid folic synthe-
sis (trimethoprim and sulfonamides). Bacteria can be inherently resistant
to a specific family of antimicrobials for various reasons: for example,
mycoplasmas are naturally resistant to β-lactam antibiotics because they
have no cell wall, and Gram-negative bacteria are intrinsically resistant to
Functionalized Nanomaterials for the Management of Microbial Infection.DOI:http://dx.doi.org/10.1016/B978-0-323-41625-2.00001-6
1
© 2017Elsevier Inc. All rights reserved.
2 CHAPTER 1 Resistance to Antibiotics and Antimicrobial Peptides
macrolides as these molecules are too large to enter the bacteria through
their cell wall. Antimicrobial resistance can be acquired in previously sus-
ceptible species, either by mutations, such as modifications of the target
DNA-gyrase which renders Enterobacteriaceae resistant to quinolones or
fluoroquinolones. Mutations can also result in the increased expression
of efflux pumps able to export one or several classes of antimicrobials.
Bacteria can also acquire resistance genes from other bacteria, by conju-
gation, transformation, or transduction. The acquired genes can encode
antibiotic-inactivating enzymes (e.g., β-lactamases and aminoglycosides-
hydrolyzing enzymes) or modified molecules which are no longer the
target of the antibiotic (e.g., altered penicillin-binding-protein PBP2a
encoded by the mecA gene in Staphylococcus aureus resistant to methicil-
lin), protect the target (e.g., tet(O) gene in Campylobacter spp. encoding a
protein protecting the ribosome against tetracycline) or a new efflux pump
(e.g., tet(A) gene in Escherichia coli encoding a tetracycline efflux pump).
The polypeptide antibiotics belonging to the polymyxin group were dis-
covered in the 1940s and were first used in both human and animal medi-
cines. Polymyxins are non-ribosomal cyclic lipopeptides mainly used from
the late 1950s as a topical treatment in human medicine. The polymyxin
E (colistin) has been used particularly for the treatment of Gram-negative
bacterial infections. However, in the 1970s, clinical use of these molecules
was limited due to their serious nephrotoxicity and neurotoxicity after par-
enteral administration under systematic use [1]. Because of this toxicity,
the use of polymyxins soon decreased, but colistin remained in frequent
use in animals, mainly for the control of enteric infections [2]. Recently
the emergence of bacteria resistant to most antibiotic families, including
carbapenems, renewed the interest for colistin as a last-resort treatment
option for infections caused by multidrug-resistant Enterobacteriaceae,
Pseudomonas aeruginosa, and Acinetobacter baumannii [3].
The basic structure of polymyxins is composed of a cyclic decapeptide
bound to a fatty acid chain at amino terminus. Polymyxin B and poly-
myxin E have almost identical primary sequence with difference at posi-
tion 6 where D-Phe (D-phenylalanine) in polymyxin B is replaced by
d-Leu (d-leucine) in polymyxin E (Fig. 1.1) [4]. The biosynthetic gene
cluster of polymyxin is called pmx cluster, including five open reading
frames, namely, pmxA, pmxB, pmxC, pmxD, and pmxE. Synthesis of poly-
myxin implies three polymyxin synthetases, PmxA, PmxB, and PmxE, and
transported by two membrane transport proteins, PmxC and PmxD. The
polymyxin structure determines its activity, the assembly order of modules
for amino acid during biosynthesis of polymyxin is PmxE–PmxA–PmxB,
the fatty acid: 6-methyloctanoic acid or isooctanoic acid; Thr, threonine;
1.1 Resistance to Antibiotics 3
(A) 6
R
O H 5
7 N O
L-Leu L-Dab 3 NH 1
NH2 L-Dab 2 L-Dab
H3HC3C NH O HN NHH2 O HN O CH3 R
NH N N
O N H
H O
NH2 O HO CH3
L-Dab O NH L-Dab L-Thr
8 OO NH 4 2
L-Dab HN
CH
9 H 3
HN
2 Polymyxin B: R6= D-Phe
L-Thr OH
Polymyxin E: R6= D-Leu
10
(B) Inner membrane
Polymyxin
PmxE synthetase
5 C-domain
γ-NH2
γ-NH2 γ-NH2 6 7
(α)L-Dab R L-Leu
Fatty acid (α)L-Dab L-Thr (α)L-Dab (α,γ)L-Dab
1 2 3 4 L-Thr (α)L-Dab (α)L-Dab
10
T-domain C-domainγ-N9H2 γ-N8H2
PmxB synthetase PmxA synthetase
Membrane transport proteins;
PmxC and PmxD
Polymyxin B: R6=D-Phe
Polymyxin E: R6=D-Leu
■■FIGURE 1.1 Chemical structure of polymyxin (A); polymyxin biosynthesis in Paenibacillus polymyxa (B). Adapted from Yu Z, Qin W, Lin J, Fang S, Qiu J. Antibacterial
mechanisms of polymyxin and bacterial resistance. BioMed Res Int 2015;679109. doi:10.1155/2015/679109.
Phe, phenylalanine; Leu, leucine; Dab, α,γ-diaminobutyric acid, α and γ
refer to the respective—NH involved in peptide linkage (Fig. 1.1).
2
Colistin is a bactericidal drug that binds to phospholipids in the outer cell
membrane of Gram-negative bacteria and to lipopolysaccharide (LPS), by
a hydrophobic interaction between the nine-carbon fatty acid side chain
of colistin and the fatty acid portion of lipid A. It competitively displaces
divalent cations from the phosphate groups of membrane lipids, which
leads to disruption of the outer cell membrane, leakage of intracellular
contents, and bacterial death (Fig. 1.2).
4 CHAPTER 1 Resistance to Antibiotics and Antimicrobial Peptides
■■FIGURE 1.2 Antimicrobial mode of action of polymyxin against Gram-negative bacterial membranes. LPS, Lipopolysaccharide. Adapted from [5] Biswas S, Brunel JM,
Dubus JC, Reynaud-Gaubert M, Rolain JM. Colistin: an update on the antibiotic of the 21st century. Expert Rev Anti-infect Ther 2012;10(8):917–34.
Resistance to polymyxins has been investigated in intrinsically resistant
bacterial species, in vitro mutants and in clinical isolates. The electrostatic
interaction between positively charged Dab residues, on polymyxin, and
negatively charged phosphate groups, on lipid A of LPS, represents the
critical step of bactericidal activity of polymyxins. Reduction of this ini-
tial electrostatic attraction can occur when net negative charge of the bac-
terial outer membrane (OM) is reduced via lipid A modification, implying