Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_6035_Библиотеки_им_академика_М_И_Перельмана.pdf
63
Recent studies have shown that natural agents derived from plants can disrupt the
biolms of clinically relevant bacteria. For example, the medicinal plants Terminalia
bellerica, Kingiodendron pinnatum, Celastrus paniculatus, Melastoma malabathricum,
Schleichera oleosa, and Garcinia gummi-gutta were tested against Pseudomonas aeruginosa
biolms. Results showed that all tested plants showed antibacterial activity, whereas T.
bellerica inhibited biolm production and other virulence factors of P. aeruginosa, such as
exopolysaccharide and pyocyanin (Sankar Ganesh and Ravishankar Rai, 2018).
On the other hand, Wijesundara and Rupasinghe (2019) tested the antibiolm activity of
14 ethanol extracts from medicinal plants. It was shown that sage leaves, purple coneower
ower, purple coneower stem, licorice root, and slippery elm inner bark ethanolic extracts
were the most effective, with minimal biolm inhibitory concentrations ranging from 31.5
to 250 μg/ml. Additionally, scanning electron microscopy showed morphological changes
in treated biolms compared to the untreated.
Carvacrol, the main compound isolated from Origanum vulgare EO, was tested
against P. aeruginosa biolms. At 0.9–7.9 mM concentration, carvacrol reduced 1.5–3
log CFU/cm2 the biolm bacterial cells on stainless steel surfaces. Additionally, the toxin
pyocyanin, another virulence factor, was reduced up to 60% at 3.9 mM of carvacrol
concentration (Tapia-Rodriguez et al., 2017). Similarly, quercetin, a avonoid widely
found in grapes and other fruits, was tested against Listeria monocytogenes biolms. A
reduction of 1.32 and 1.94 log10 CFU/cm2 was observed after treatment with 0.2 mM of
quercetin. Also, at this concentration, extracellular protein content was reduced by 41%
compared with the control, possibly altering the bacterium’s biolm formation capacity
(Vazquez-Armenta et al., 2018).
The antimicrobial mode of action of plant-derived compounds is throughout
different mechanisms: they act mainly on microbial cells disrupting the integrity of the
cell membrane, inhibiting enzymatic activity, interfering with cell wall synthesis, and
disrupting the microbial cell’s energy production (Khameneh et al., 2019). Additionally,
some antimicrobial compounds can interfere with microbial communication and quorum
sensing (QS), reducing the pathogen’s ability to coordinate activities and promote
virulence (Gutierrez-Pacheco et al., 2019; Vazquez-Armenta et al., 2020). Overall, plants’
antimicrobial mechanism of action involves diverse compounds that act on different targets
in the microbial cell, making them a valuable source of natural antimicrobial agents with
potential applications in medicine and agriculture.
4.3 MARINE SOURCES AS ANTIMICROBIAL AGENTS
The marine environment covers almost 70% of the earth’s surface; in this complex ecosystem,
various marine entities have been identified, including animals, plants, associated microbes,
as well as microorganisms originated from marine sediment and water (Sathish and Kokati,
2012; Srinivasan et al., 2021). These organisms are rich sources of bioactive compounds;
however, most have not been explored in the search for new drugs and pharmacologically
active substances (Sathish and Kokati, 2012). In underwater ecosystems, organisms are
exposed to extreme environmental conditions caused by high salt concentrations in the water,
64
oxygen concentrations, extreme temperatures, ocean currents, light penetration, and radiation
exposure (Ribeiro et al., 2022). These factors stimulate the production of a large arsenal of
bioactive chemical compounds in marine organisms that are considered essential for discovering and developing new antimicrobial agents. Research has shown that marine organisms
are a source of various secondary metabolites with antimicrobial activity such as flavonoids,
terpenoids, phenolic compounds, alkaloids, fatty acids, peptides, carbohydrates, polyketides,
and steroids (Kurhekar, 2020). Table 4.3 depicts the antimicrobial effect of marine sources.
In this sense, the antimicrobial activity of the green, brown, and red seaweed has been
demonstrated. Moubayed et al. (2017) reported that brown and green algae obtained from
Saudi Arabia Red Sea and Arabian Gulf showed antibacterial activity against diverse Grampositive (S. aureus, S. xylosus, MRSA, B. subtilis, E. faecalis) and Gram-negative bacteria
(E. coli, P. aeruginosa, Salmonella sp. clinical isolate, and K. pneumoniae). The acetone
extract of the brown seaweed Sargassum latifolium B showed great antimicrobial effect
against Salmonella sp. and S. xylosus, meanwhile, the methanolic extract of S. latifolium
B inhibited more efciently the growth of MRSA, S. aureus, and B. subtilis. Methanolic
extract of Sargassum platycarpum showed more antimicrobial activity in comparison with S.
platycarpum methanolic extract, particularly against E. coli, B. subtilis, and S. xylosus. On the
other hand, acetone and methanolic extract of the fresh green seaweed Cladophora socialis
showed more effective antimicrobial activity in relation to the acetone and methanolic extract
of the dry C. socialis, this effect was observed particularly against Gram-negative bacteria.
The antimicrobial activity of the chloroform and methanol extract of the Malasian
green seaweeds Caulerpa racemosa and Caulerpa lentillifera known as “sea grapes”
against MRSA and neuropathogenic E. coli K1 has been reported. Chloroform extract of
C. racemosa was the most effective to inhibit the growth of the Gram-positive bacteria
MRSA. Likewise, chloroform extract from C. lentillifera more efciently reduced the
growth of MRSA in comparison to the other extracts. The chemical analysis by liquid
chromatography–mass spectrometry of the C. racemosa chloroform extract allowed to
identify diverse polyunsaturated and monounsaturated fatty acids, terpenes, and alkaloids,
such as pristimerin, caulerpin, 5(S)-HETE lactone, isoamijiol, 12-oxo-10Z-octadecenoic
acid, among others (Yap et al., 2019).
The antimicrobial activity of the extracts and isolated compounds of the brown seaweed
Dictyota acutiloba J. Ag. has been investigated. Chloroform and acetone extracts of D.
acutiloba showed antimicrobial activity against diverse bacteria such as MRSA, methi-
cillin-susceptible S. aureus (MSSA), Enterobacter sp., S. typhi MTCC733, P. aeruginosa
MTCC741, B. subtilis, and K. pneumoniae MTCC109. The purication of chloroform
and acetone extracts by chromatographic column led to the isolation of two antimicrobial
compounds, A1 and C1. In the same way, the two isolated compounds reduced effectively the growth of MRSA, MSSA, Enterobacter sp., S. typhi MTCC733, P. aeruginosa
MTCC741, B. subtilis, and K. pneumoniae MTCC109 (Jebakumar Solomon and Satheeja
Santhi, 2008). Busetti et al. (2015) demonstrated that the extracts and fractions from the
marine brown alga Halidrys siliquosa possess antimicrobial and antibiolm effect against
diverse human pathogenic bacteria such as S. aureus ATCC 29213, S. haemolyticus NCTC
11042, S. pyogenes NCTC 8306 (A TCC 12204), S. pneumoniae NCTC 7465, P. aeruginosa
NCTC 12903 (ATCC 27853), among others.
TABLE 4.3 Antimicrobial Effect of Marine Sources
Analyzed Sources Extraction Solvent Concentration Microorganism Effect References
Caulerpa racemosa
Caulerpa lentillifera
Sargassum latifolium
Sargassum platycarpum
Chloroform 250 μg/ml
Methanol 250 μg/ml
Water 250 μg/ml
Chloroform 250 μg/ml MRSA
Methanol 250 μg/ml
Water 250 μg/ml
Acetone 100 μl
Methanol 100 μl
Acetone 100 μl
⏎
250 μg/ml
250 μg/ml
250 μg/ml
250 μg/ml
250 μg/ml
100 μl
MRSA
E. coli K1
MRSA
E. coli K1
MRSA
E. coli K1
E. coli K1
MRSA
E. coli K1
MRSA
E. coli K1
K. pneumoniae
P. aeruginosa, E. coli,
E. feacalis, B. subtilis,
S. aureus, MRSA
Salmonella sp., S. xylosus
E. coli, K. pneumoniae,
P. aeruginosa, MRSA,
B. subtilis, E. feacalis,
S. aureus, S. xylosus
Salmonella sp.
E. coli, K. pneumoniae,
P. aeruginosa, MRSA,
B. subtilis, E. feacalis,
S. aureus, S. xylosus
Salmonella sp.
Growth inhibition
Growth inhibition
No effect
Growth inhibition
Growth inhibition
No effect
No effect
Growth inhibition
No effect
Growth inhibition
No effect
Growth inhibition
Yap et al. (2019)
Moubayed et al. (2017)
65
TABLE 4.3
Analyzed Sources Extraction Solvent Concentration Microorganism Effect References
Sargassum platycarpum
Cladophora socialis green
Cladophora socialis green
Cladophora socialis dry
Cladophora socialis dry
(Continued)
Methanol 100 μl
Acetone 100 μl
Methanol 100 μl
Acetone 100 μl
Methanol 100 μl
26.33 μg/ml
28.46 μg/ml
30.52 μg/ml
E. coli, K. pneumoniae,
P. aeruginosa, MRSA,
B. subtilis, E. feacalis,
S. aureus, S. xylosus
E. coli, K. pneumoniae,
P. aeruginosa, MRSA,
B. subtilis, E. feacalis,
S. aureus, S. xylosus
Salmonella sp.
E. coli, K. pneumoniae,
P. aeruginosa, MRSA,
B. subtilis, E. feacalis,
S. aureus, S. xylosus
Salmonella sp.
E. coli, K. pneumoniae,
P. aeruginosa, MRSA,
B. subtilis, E. feacalis,
S. aureus, S. xylosus
Salmonella sp.
K. pneumoniae,
P. aeruginosa,
Salmonella sp., E.
feacalis
S. aureus, S. xylosus
MRSA, B. subtilis
S. aureus
K. pneumoniae
P. aureginosa
No effect
Growth inhibition
No effect
Growth inhibition
No effect
Growth inhibition
No effect
Growth inhibition
No effect
Growth inhibition
66
TABLE 4.3 (Continued)
Analyzed Sources Extraction Solvent Concentration Microorganism Effect References
Dictyota acutiloba
A1 from Dictyota acutiloba
C1 from Dictyota acutiloba
Halidrys siliquosa
Chloroform 27.71 μg/ml
17.23 μg/ml
21.25 μg/ml
24.54 μg/ml
24.37 μg/ml
27.95 μg/ml
29.85 μg/ml
26.25 μg/ml
0.50 μg/ml
0.60 μg/ml
0.69 μg/ml
0.71 μg/ml
0.81μg/ml
0.90 μg/ml
0.70 μg/ml
0.50 μg/ml
0.60 μg/ml
0.70 μg/ml
0.72 μg/ml
0.83 μg/ml
0.89 μg/ml
0.68 μg/ml
Methanol 0.3125 mg/ml
0.1562 mg/ml
0.1562 mg/ml
Enterobacter
B. subtilis
S. typhi
MRSA
S. aureus
K. pneumoniae
P. aureginosa
Enterobacter
B. subtilis
S. typhi
MRSA
S. aureus
K. pneumoniae
P. aureginosa
Enterobacter
B. subtilis
S. typhi
MRSA
S. aureus
K. pneumoniae
P. aureginosa
Enterobacter
S. aureus
S. aureus
MRSA
Growth inhibition
Growth inhibition
Growth inhibition
Growth inhibition
Busetti et al. (2015)
67
TABLE 4.3
Analyzed Sources Extraction Solvent Concentration Microorganism Effect References
(Continued)
0.1562 mg/ml
0.3125 mg/ml
0.1562 mg/ml
0.1562 mg/ml
0.625 mg/ml
0.1562 mg/ml
0.0391 mg/ml
0.0391 mg/ml
0.3125 mg/ml
1.25 mg/ml
2.5 mg/ml
2.5 mg/ml
5 mg/ml
0.3125 mg/ml
0.3125 mg/ml
0.1562 mg/ml
0.3125 mg/ml
0.3125 mg/ml
0.3125 mg/ml
0.3125 mg/ml
1.25 mg/ml
0.3125 mg/ml
0.3125 mg/ml
0.0781 mg/ml
0.625 mg/ml
MRSA
MRSA
S. epidermidis
S. epidermidis MRSE
S. haemolyticus
S. pyogenes
S. pneumoniae
E. faecalis
P. mirabilis
P. aeruginosa
P. aeruginosa
E. coli
S. aureus
MRSA
MRSA
MRSA
S. epidermidis
S. epidermidis
S. epidermidis MRSE
S. haemolyticus
S. pyogenes
S. pneumoniae
E. faecalis
P. aeruginosa
Bactericidal effect
68
TABLE 4.3
Analyzed Sources Extraction Solvent Concentration Microorganism Effect References
Myticalin C9 from Mytilus sp.
Myticalin D2 from Mytilus sp.
Myticusin-beta from Mytilus
coruscus
Ubiquitin from Crassostrea gigas
EeCentrocin 1 from Echinus
esculentus
EeCentrocin 2 from Echinus
esculentus
EeStrongylocin 2
from Echinus esculentus
Crustin from Portunus pelagicus
Pestalotiopsis sydowiana
(Continued)
5 mg/ml
5 mg/ml
5 mg/ml
8 μM
4 μM
2 μM
4 μM
4 μM
2 μM
16–32 μM
2 μM
9.2 mm
0.6 μM
0.78 μM
0.78 μM
1.56 μM
50 μg/ml
1000 μg/ml
500 μg/ml
P. aeruginosa, E. coli
P. aureginosa
E. coli
A. baumannii
S. aureus
B. subtilis
P. aureginosa
E. coli
A. baumannii
S. aureus
B. subtilis
P. aureginosa
P. aureginosa
P. aureginosa
P. aureginosa
P. aureginosa
P. aureginosa
P. aureginosa
P. aureginosa
Growth inhibition
Growth inhibition
Growth inhibition Ribeiro et al. (2022)
Growth inhibition
Reduction of virulence
phenotypes: production of
pyocyanin, chitinase,
Ribeiro et al. (2022)
Coppola et al. (2023)
Parasuraman
69
et al. (2020)
TABLE 4.3
Analyzed Sources Extraction Solvent Concentration Microorganism Effect References
Cyclo(-Leu-Pro) (CLP) from
Pestalotiopsis sydowiana
4-hydroxyphenylacetamide
(4-HPA) from Pestalotiopsis
sydowiana
Cladodionen from Cladosporium
sp. Z148
HNM from Streptomyces
variabilis
A101 from Vibrio sp.
A101 from Vibrio sp.
Notes: MRSA: methicillin-resistant S. aureus; MRSE: methicillin-resistant S. epidermidis.
(Continued)
250 μg/ml
125 μg/ml
400 μM
200 μg/ml
100 μg/ml
100 μg/ml
P. aureginosa
P. aureginosa
P. aureginosa
E. coli
V. cholerae
S. aureus
P. aeruginosa
S. aureus
P. aeruginosa
S. aureus
protease, elastase,
and staphylolytic
activity Reduction of:
exopolysaccharides,
rhamnolipids, and alginate
Growth inhibition
Growth inhibition
Biofilm formation
inhibition Downregulation
of the mRNA expression:
lasR, lasI, lasB, rhlR,
rhlI, rhlA, pqsR, pqsA
Biofilm formation
inhibition
Biofilm formation
inhibition
Biofilm formation
inhibition
Biofilm formation
inhibition
Biofilm formation
inhibition
Reduction of total
surface-bound biomass
Reduction of total
surface-bound biomass
Wang et al. (2020b)
Vaikundamoorthy et al.
(2019)
Jiang
et al. (2011)
70
71
Diverse bioactive metabolites derived from marine sources serve as valuable agents
against P. aeruginosa, some of them act as antimicrobial and others reduced the virulence
factors (Coppola et al., 2022). In the blue mussel Mytilus sp. diverse myticalin peptides
with antimicrobial potential against P. aeruginosa has been identied (A5, A8, C9, and
D2). In the same way, myticusin-beta has been identied in Mytilus coruscus as a bioactive
peptide with antimicrobial potential against P. aeruginosa. Crassostrea gigas (pacic
oyster) (cgUbiquitin), Echinus esculentus (sea urchin) (EeCentrocin 1, EeCentrocin 2, and
EeStrongylocin 2), Portunu spelagicus (Crab) (crustin) are other peptide-producing marine
organisms with activity against P. aeruginosa (Ribeiro et al., 2022). The antimicrobial effect
of myticalin peptides against E. coli ATCC 25922, A. baumannii ATCC 19606, S. aureus
ATCC 25923, and B. subtilis ATCC 6051 has been reported as well (Leoni et al., 2017).
Other marine organisms have been investigated for their ability to reduce virulence
factors and regulate QS. A study carried out by Parasuraman et al. (2020) showed that
the marine fungal Pestalotiopsis sydowiana extract induce antimicrobial effect on P.
aeruginosa through the regulation of virulence phenotypes such as the production of
pyocyanin, chitinase, protease, elastase, and staphylolytic activity viaQS modulation. In
addition, P. sydowiana extract inhibited the biolm formation and reduced the produc-
tion of exopolysaccharides, rhamnolipids, and alginate. Cyclo(-Leu-Pro) (CLP) and
4-hydroxyphenylacetamide (4-HPA) were identied as potential bioactive compounds in P.
sydowiana PPR. In-silico studies showed that CLP and 4-HPA interact with the QS receptor
proteins LasR and RhlR similarly to its ligands. On the other hand, the hybrid polyketide
cladodionen isolated from the marine fungus Cladosporium sp. Z148 has been identied as
a novel QS inhibitor on P. aeruginosa. The compound demonstrated signicant reductions
in biolm formation, motility, and mRNA expression of genes associated with QS. These
genes included autoinducer synthases (rhlI, lasI, and pqsA), receptor proteins (rhlR, lasR,
and pqsR), and virulence factors (rhlA and lasB). Molecular docking analysis revealed that
cladodionen exhibited superior binding afnity compared to the natural QS ligands, LasR,
and PqsR (Wang et al., 2020).
In other studies, the antimicrobial effects of bioactive compounds derived from marine
bacteria have been described. Ramalingam et al. (2019) explored the antibiolm activity
of 1-hydroxy-1-norresistomycin (HNM) obtained from the coral mucus-associated actinomycete Streptomyces variabilis. In-vitro studies showed that HNM inhibited the biolm
formation of V. cholerae, E. coli, and S. aur eus. HNM also induced a reduction of bacterial
adherence and aggregation by altering surface hydrophobicity; likewise, HNM induced
damage in the bacterial 3D architecture. By molecular docking the capability of HNM
to interact with E. coli (2K9S and 3DYM), V. cholerae (1YG2 and 4KKP) and S. aureus
(2FNP and 3EIF) proteins involved in the biolm formation has been demonstrated. In
their study, Jiang et al. (2011) successfully isolated the antimicrobial exopolysaccharide
A101 from the supernatant of the marine bacterium Vibrio sp. In-vitro studies showed anti-
biolm activity of A101 against a wide range of Gram-negative and Gram-positive bacteria
(P. aeruginosa, E. coli, Actinobacillus actinomycetemcomitans, S. aureus, S. epidermidis,
and E. faecalis). Likewise, A101 increased the antibiotic sensitive of bacteria biolms of P.
aeruginosa and inhibited the cell surfaces adherences and the intracellular adhesion of P.
aeruginosa and S. aureus.
72
Taken together, the ndings demonstrated that marine organisms are important sources
for the search for new antimicrobial agents against pathogenic bacteria of clinical relevance
in humans. However, it is necessary to evaluate the effectiveness of these molecules using
in-vivo models and to establish their pharmacokinetic, pharmacodynamic, and toxicity
prole.
4.4 ANTIMICROBIAL PRODUCTS DERIVED FROM MICROORGANISMS
Microorganisms are particularly notable for their ability to produce secondary metabolites
with antibacterial, antifungal, and cytotoxic activity . These metabolites are synthesized and
released to help microorganisms grow in various environmental conditions. This characteristic makes them a promising source of new antimicrobial substances that could combat
the problem of antimicrobial resistance (Amaning Danquah et al., 2022). In this way,
different studies have been demonstrated the antimicrobial effect of metabolites produced
by microorganism (Table 4.4).
Lantibiotics represent a group of antimicrobial peptides produced by ribosomes. They
are distinguished by the presence of lanthionine and β-methyllanthionine, which are
unique amino acid residues formed through posttranslational modications. The MICs
of lantibiotic lacticin (3147) and nisin against the S. aureus strains vancomycin-resistant
enterococci (VRE), methicillin-resistant (MRSA), intermediate resistance to vancomycin
(VISA), heterogeneous vancomycin-intermediate (hVISA), and methicillin-susceptible
(MSSA), were determined. Lacticin 3147 demonstrated high inhibitory activity against
VRE (MIC = 1.9–7.7 mg/l), and varying levels of activity against MRSA (MIC = 1.9–15.4
mg/l), hVISA (MIC = 15.4–30.9 mg/l), and VISA (MIC = 61.8 mg/l). On the other hand,
nisin showed better activity against S. aureus strains in general (MRSA and laboratory
strains, MIC = 0.5–4.1 mg/l; VISA and hVISA, MIC = 2–8.3 mg/l), but was less effective
against VRE (2–8.3 mg/l) compared to lacticin 3147 (Piper et al., 2009).
Lactobacillus crispatus also produces a bacteriocin known as Helveticin-M, which
has shown antimicrobial activity against S. aureus, S. saprophyticus, and Enterobacter
cloacae at 200 μg/ml (Sun et al., 2018). Additionally, the mode of action of Helveticin-M
depends on the bacterial species targeted. Helveticin-M disrupted Gram-positive bacteria’ s
cell wall, while disorganized Gram-negative bacteria’s outer membrane, causing a change
in their surface.
Additionally, Helveticin-M modied the inner membrane, leading in the release of
intracellular ATP and depolarization of the membrane potential of the target bacteria, as
veried through cell population analysis. Although Helveticin-M increased cell membrane
permeability, it had no impact on cytosolic enzymes, suggesting a sublethal injury . Consequently, the mode of action of Helveticin-M is bacteriostatic rather than bactericidal (Sun
et al., 2018).
Field et al. (2015) investigated the effectiveness of semipuried preparations containing
either nisin A or an enhanced bioengineered derivative, nisin V, against various strains of
L. monocytogenes. The ndings showed that nisin V exhibited twice the activity (MIC
of 39 μg/ml) compared to nisin A (MIC of 78 μg/ml) against L. monocytogenes EGDe,