2. Treatment of Listeriosis
L. monocytogenes is susceptible to many different antimicrobials that are used for gram-positive bacteria
[23][24][225,226]. These include β-lactams, gentamicin, erythromycin, tetracycline, rifampicin, and vancomycin. On the other hand,
L. monocytogenes is naturally resistant to cephalosporins, nalidixic acid, and polymyxin E
[23][225]. Furthermore, most isolates are not susceptible to fluoroquinolones and cephalosporins of the third (e.g., cefotaxime) and fourth (cefepime) generations, nor to fosfomycin, oxacillin, and lincosamides
[25][227]. High resistance to tetracyclines has been also reported in a few strains
[23][26][225,228]. Antimicrobial resistance/susceptibility of
L. monocytogenes strains varies widely and depends on sampling sites, time of sampling, source of isolates, and geographical origin.
In 1988, the first multiresistant (i.e., showing resistance to three or more classes of antimicrobials)
L. monocytogenes strain of human origin was described in France
[27][229]. It displayed resistance to chloramphenicol, erythromycin, streptomycin, and tetracycline. The genes responsible for resistance to these antibiotics were located on a 37 kb plasmid. Since then, several other
L. monocytogenes strains with antimicrobial multiresistance patterns have been isolated from different clinical, food, and environmental origins
[26][28][29][30][31][228,230,231,232,233].
Based on
L. monocytogenes in vitro antimicrobial resistance results, treatment of severe listeriosis with β-lactams (penicillin or ampicillin) alone or combined with an aminoglycoside (e.g., kanamycin or gentamicin) is recommended
[28][32][230,234]. Additionally, in cases of reduced sensitivity or resistance of the strains to β-lactams, other antimicrobial substances that are effective against gram-positive bacteria may be used, e.g., tetracyclines, erythromycin, chloramphenicol, vancomycin, and trimethoprim/sulfamethoxazole
[32][234]. The latter antimicrobials are recommended for patients with an allergy to penicillin, whereas persons with bacteremia due to
L. monocytogenes may be treated with vancomycin
[32][234]. Furthermore, erythromycin can be used in patients with an allergy to ampicillin and/or gentamicin
[33][214]. During pregnancy of
L. monocytogenes-infected women, ampicillin or erythromycin intravenously or amoxicillin orally are used for at least 14 days, or even until delivery
[34][224]. When the woman does not tolerate penicillin or amoxicillin, trimethoprim with sulfamethoxazole are the drugs of choice
[34][224]. However, trimethoprim can damage the fetus in the early stages of pregnancy, including its heart and nervous system; therefore, patients with penicillin intolerance expecting a baby can be treated with erythromycin that is safe for fetus
[35][36][235,236].
An increasing resistance of
L. monocytogenes against antimicrobials, including antibiotics, led to the search for alternative therapies
[37][237]. One of them is the application of bacteriocins, which are natural peptides produced by various bacteria
[38][39][238,239]. Several bacteriocins are stable in gastrointestinal conditions, possess a low toxicity, and show a significant effect against pathogenic bacteria, including antibiotic-resistant strains
[40][41][240,241]. It was shown that nisin (produced by
Lactococcus lactis) and pediocin (secreted by
Pediococcus acidilactici), demonstrated inhibitory activity against
L. monocytogenes both in vitro and in vivo
[42][43][242,243].
Another group of antibacterial substances that are promising alternatives to antibiotics are natural products of plant origin that possess different mechanisms of action directed towards increasing membrane permeability, decreasing its integrity, or disruption of bacterial efflux pumps
[44][244]. Among them are terpenoids such as limonene and carvacrol, which has been shown to be effective against
L. monocytogenes [45][46][245,246].
The efficacy of other phytochemicals such as trans-cinnamaldehyde, carvacrol, and thymol in reducing
L. monocytogenes virulence was demonstrated using the
Galleria mellonella invertebrate model
[47][247].
Although all these plant products demonstrated antibacterial activity, their application in treatment of listeriosis requires further mammalian and clinical studies
[44][244].
3. Prevention of Listeriosis
Currently, there is no effective vaccine against listeriosis, although some experiments have shown that cell-based and subunit-based immunoprepartions lacking cytotoxicity and pathogenicity may be highly protective
[48][49][50][248,249,250]. Furthermore,
L. monocytogenes is often applied as a vaccine vector for protection against other pathogens as well as in cancer therapy
[51][52][251,252]. Therefore, prevention of
L. monocytogenes infection is the most important way to control the disease, since the bacterium is widely distributed in the environment, including in food-production facilities
[3][53][3,253]. It has been revealed that
L. monocytogenes is able to survive there for a long time due to inadequate cleaning and disinfection of food production equipment or insufficient supervision of employees
[17]. Most sporadic listeriosis cases and large outbreaks were due to the consumption of contaminated food with these bacteria, especially ready-to-eat food of animal origin
[17]. Listeriosis is a typical zoonotic food-borne disease, although it may be also transmitted through direct contact with infected animals or contaminated environments
[21][22][21,22].
There are studies on the prevention of
L. monocytogenes infection by the use of probiotics
[54][55][56][57][58][254,255,256,257,258]. Probiotic bacteria, e.g., lactobacilli, have shown positive effects in mice by producing bacteriocin or by changing the host gene expression or
L. monocytogenes transcriptome
[59][259]. Drolia et al. demonstrated that
Lactobacillus casei expressing
Listeria adhesion protein (LAP) colonized the intestine, adhered to the heat shock protein 60 (Hsp60) receptor, and excluded
L. monocytogenes from intestinal colonization and systemic dissemination
[57][257]. Furthermore, such probiotic bacteria were also able to prevent fetoplacental transmission of the pathogen in a pregnant guinea pig model
[58][258]. Another study of Mathipa et al. showed that in
L. casei expressing
L. monocytogenes, InlA and InlB inhibited adhesion, invasion, and translocation of
L. monocytogenes through enterocyte-like Caco-2 cells
[56][256]. All these results suggest that molecularly recombinant probiotic bacteria possessing
Listeria virulence traits may be a potential approach for prevention of human listeriosis.
The key aspect in prevention of listeriosis is proper food preparation, handling, and storage to avoid its contamination or cross-contamination and then consumption by humans
[60][61][62][260,261,262]. According to the European Union food law regulation, the criteria for
L. monocytogenes varies on the food category and intended consumer population
[63][263]. Generally, there is zero tolerance for ready-to-eat foods for infants and for food of special medical purposes, and up to 100 cfu/g for other ready-to-eat foods.
Crucial factors for listeriosis prevention cover rapid and specific detection of
L. monocytogenes in food with classical or alternative methods and determination of the infection sources
[64][264].
L. monocytogenes is not only able to persist, but also multiply in a wide range of adverse conditions present in food production environments and create biofilms on various surfaces. All these features make it difficult to eliminate the bacteria and enable them to survive there for a long time
[65][265]. Therefore, efficient methods of removal of the pathogen from the food industry environment, which are fundamental for ensuring the safety of food production, should be developed and applied
[66][266].