ISSN 0003-6838, Applied Biochemistry and Microbiology, 2018, Vol. 54, No. 3, pp. 277–287. © Pleiades Publishing, Inc., 2018.
Original Russian Text © T.V. Fedorova, D.V. Vasina, A.V. Begunova, I.V. Rozhkova, T.A. Raskoshnaya, N.I. Gabrielyan, 2018, published in Prikladnaya Biokhimiya i Mikrobiologiya,
2018, Vol. 54, No. 3, pp. 264–276.
Antagonistic Activity of Lactic Acid Bacteria Lactobacillus spp.
against Clinical Isolates of Klebsiella pneumoniae
T. V. Fedorova
*, D. V. Vasina
, A. V. Begunova
, I. V. Rozhkova
T. A. Raskoshnaya
, and N. I. Gabrielyan
Bach Institute of Biochemistry, Research Center of Biotechnology, Russian Academy of Sciences, Moscow, 119071 Russia
All-Russia Research Institute of Dairy Industry, Moscow, 115093 Russia
V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, 123182 Russia
Received October 20, 2017
Abstract⎯The screening of three strains of lactic acid bacteria identified as Lactobacillus rhamnosus, Lacto-
bacillus reuteri, and Lactobacillus helveticus showed significant antagonistic activity against Klebsiella pneu-
moniae strains characterized by multiple antibiotic resistance. Lactobacilli cocultivated with the Klebsiella
strains inhibited their growth 20 to 86% on the first and second days, respectively. Exoproteome analysis of
L. rhamnosus cocultivated with K. pneumoniae revealed the induction of peptidoglycan hydrolases, including
extracellular lytic transglycosylases, family II (MltA), and endopeptidases capable of disrupting the peptido-
glycan bacterial cell wall.
Keywords: Klebsiella pneumoniae, antibiotic resistance, antagonistic activity, probiotics, Lactobacillus rham-
nosus, secretome, peptidoglycan hydrolases
The preventive care and treatment of nosocomial
(hospital) infections are currently of significant
importance all over the world. Nosocomial infections
caused by antibiotic resistant microorganisms are of
particular interest. The risks of hospital infection are
constantly increasing [1, 2]. For example, in the
United States, this problem is considered as a threat
national security. In 2017, the World Health Organiza-
tion (WHO) published a list of antibiotic resistant bac-
teria with the highest threat to human health . The
list was created as part of a WHO program to control
microorganism resistance to antimicrobial drugs. It is
intended for the coordination and stimulation of
research to invent new drugs.
Gram-negative bacteria are a wide group of micro-
organisms that are capable of causing heavy clinical
infections, pneumonia, and sepsis, which can result in
patient deaths. These microorganisms are more danger-
ous in hospitals, since their infections can be propa-
gated in various departments: surgery, burns, oncology,
urology, intensive care, intensive therapy, and neonatal.
In this case, hospital strains penetrate a patient organ-
ism and cause infection via immediate patient contact,
air, medical equipment, or drugs. Infections caused by
hospital strains are difficult to treat, since their agents
are characterized by multidrug resistance to antibiotics.
In this respect, gram-negative strains of the Klebsiella
genus are the most dangerous, not only because they
have multiple antibiotic resistance but also because
their resistance determinants circulate amongst differ-
ent strains and become a real disaster.
The search for new antimicrobial drugs is a prerog-
ative for efficient control of the antibiotic resistance of
opportunistic infections and the development of opti-
mal therapy for infectious diseases. Studies on the
antimicrobial potential of probiotic lactic acid bacteria
is one current approach [4, 5].
Microorganisms of the Lactobacillus genus are
widespread in nature, and some species are important
representatives of human microbiota. Lactobacilli are
interesting in that they can be used for health care,
preventive medicine, and the treatment of many dis-
eases [6, 7]. Due to the production of organic acids
(lactic, acetic, and propionic acids), peroxides, and
bacteriocins, many lactobacillus strains show high
antagonistic activity with respect to many microbial
pathogens . New knowledge of the biological prop-
erties of lactobacilli are required to create probiotic
products and their drug derivatives.
The goal of this work is to study the antagonistic
effect of a collection of lactobacillus strains on antibi-
otic-resistant Klebsiella spp., strains that are agents of