Posts Tagged ‘L monocytes’

In the name of Translation from a food born pathogen to  a friendly vaccine: Listeria monocytogenes

Curator: Demet Sag, PhD, CRA, GCP

Is it a far fetch? Friend or Foe?


Listeria monocytogenes is a Gram-positive, facultative intracellular pathogen bacterium.  It is used as a prototypes for an experimental model to understand the fundamental processes of adaptive immunity and virulence.  10 species of L. monocytogenes is identified in both humans and animals, L. ivanovii mainly infects ungulates (eg. sheep and cattle), while other species (L. innocua, L. seeligeri, L. welshimeri, L. grayi, L. marthii, L. rocourtiae, L. fleischmannii and L. weihenstephanensis) are essentially saprophytes. Within the species of L. monocytogenes, several serovars (e.g., 4b, 1/2a, 1/2b and 1/2c) are highly pathogenic and account for a majority of clinical isolations.

Gram-negative bacteria has inner and outer membranes and they are most studied; yet mechanics of protein secretion across the single cell membrane of Gram-positive is not. The protein secretion in gram positive bacteria is complex not only it requires translocation of polypeptides across the bacterial membrane into the highly charged environment of the membrane-cell wall interface but also folding specifically. As a result, protein folding mechanism and stability investigated for the role of PrsA2 and PrsA-like so that optimizing the virulence and protein secretion become possible.

Pathogen: Listeriosis

Listeria monocytogenes is a food-borne pathogen determined in 1980s causing an opportunistic disease called listeriosis which is widespread in nature being part of the faecal flora of many mammals. In addition to contaminated food resources (1-10%), may occur sporadically or in outbreaks.   It can be difficult to control and may cause severe clinical outcomes, especially in pregnant women, children and the elderly. The mechanism of pathogenity based on simply altering the actin cytoskeleton structure. Infection causes a spectrum of illness, ranging from febrile gastroenteritis to invasive disease, including bacteraemia, sepsis, and meningoencephalitis.


This organisms copes well with bile acids and acidic environment such as glutamate decarboxylase and arginine deiminase systems to survive in competitive microbiome of GI.

This information may benefit developing effective vaccines, designing pharmabiotics; even including probiotics, prebiotics, or phages.



Altering dietary habit assumed to control a disease. The effects of various fatty acids on bacterial clearance and disease outcome through suppression or activation of immune responses can’t be simplified down to one or two kinds of fatty acids in foodborne pathogens. Commonly they have a specialized carbohydrate metabolism so they can utilize fatty acids of host and the host may use the end products for an energy resource. The compared food-borne pathogens include Salmonella sp., Campylobacter sp.,Shiga toxin-producing Escherichia coli, Shigella sp., Listeria monocytogenes, and Staphylococcus aureus.



This bacterium has a complex transcriptional machinery to adept, invade several types of cells, and survive. It happens through RNA-based regulation in bacteria in cell biology at the chromatin level during bacterial infection.  This includes clathrin, atypical mitochondrial fragmentation, and several hundred non-coding RNAs (ncRNAs) in the Listeria genome.  Patho-epigenetics becoming an attractive field. Improved bioinformatics may help to classify these changes under specific regulatory mechanisms and networks to determine their function and use.


The Toxin, Vaccine and Immunotheraphy

The virulence of Listeria monocytogenes mainly depends on a listeriolysin O (LLO) which is a thiol-activated, cholesterol-dependent, pore-forming toxin, and highly immunogenic. In addition, biochemically, LLO, a toxin that belongs to the family of cholesterol-dependent cytolysins (CDCs), exhibits potent cell type-non-specific toxicity and is a source of dominant CD4(+) and CD8(+) T cell epitopes. Hence, it is the major target for innate and adaptive immune responses in different animal models and humans.


As a result, during infection bacteria escape from phagocytosis, allow bacteria to infest the cells and multiply.  Thus, due to it’s naturally immunomodulation role this mechanisms is under investigation so that it can be used for cancer immunotherapies for developing immune tolerance. Since it has effective cytotoxicity.   Thus, co-administration of this toxin or using as an adjuvant with vaccine vectors are also under research.  LLO has diverse biological activities such as cytotoxicity, apoptosis induction, endoplasmic reticulum stress response, modulation of gene expression,


Since FDA approved Sipuleucel-T (Provenge, Dendreon, Seattle, WA), which consists of antigen-loaded dendritic cells (DCs), there is a boom in immunotherapy applications. Yet, there is a shortcoming of this application because of its limited scope in immune response.  However, Listeria monocytogenes (Lm) naturally targets DCs in vivo and stimulates both innate and adaptive cellular immunity. Lm-based vaccines engineered to express cancer antigens have demonstrated striking efficacy applications.



On the other hand, there is a caution to be taken in clinics since L. monocytogenes most often presents as acute bacterial meningitis, particularly in weaken immune system of patients such as elderly, already sick patients as secondary infection/opportunistic, and those with already immune fragile state. L. monocytogenes CNS the infections may present as acute bacterial meningitis, meningoencephalitis, or acute encephalitis.


References and Further readings:


PMCID: PMC3574585 PMID: 22595054

Le DT(1), Dubenksy TW Jr, Brockstedt DG. “Clinical development of Listeria monocytogenes-based immunotherapies”. 20. Semin Oncol. 2012 Jun;39(3):311-22. doi: 10.1053/j.seminoncol.2012.02.008.


PMCID: PMC3987759 PMID: 24826075

Liu D(1).“Molecular approaches to the identification of pathogenic and nonpathogenic Listeriae”.  16. Microbiol Insights. 2013 Jul 22;6:59-69. doi: 10.4137/MBI.S10880. eCollection 2013.


PMCID: PMC4385656 PMID: 25874208

Hernández-Flores KG(1), Vivanco-Cid H(2).  Biological effects of listeriolysin O: implications for vaccination. Biomed Res Int. 2015;2015:360741. doi: 10.1155/2015/360741. Epub 2015 Mar 22.


PMCID: PMC4369580 PMID: 25241232

Maertens de Noordhout C(1), Devleesschauwer B(2), Angulo FJ(3), Verbeke G(4), Haagsma J(5), Kirk M(6), Havelaar A(7), Speybroeck N(8). “The global burden of listeriosis: a systematic review and meta-analysis”. 2. Lancet Infect Dis. 2014 Nov;14(11):1073-82. doi: 10.1016/S1473-3099(14)70870-9. Epub 2014 Sep 15.


PMID: 24911203

Cossart P(1), Lebreton A(2).  “A trip in the “New Microbiology” with the bacterial pathogen Listeria Monocytogenes”. 3. FEBS Lett. 2014 Aug 1;588(15):2437-45. doi: 10.1016/j.febslet.2014.05.051. Epub 2014 Jun 6.


PMCID: PMC4005144  PMID: 24822197

Hernandez-Milian A(1), Payeras-Cifre A(1). “What is new in listeriosis?”. Biomed Res Int. 2014;2014:358051. doi: 10.1155/2014/358051. Epub 2014 Apr 14.


PMCID: PMC4179725  PMID: 25325017

Schultze T(1), Izar B(2), Qing X(1), Mannala GK(1), Hain T(1). “Current status of antisense RNA-mediated gene regulation in Listeria  monocytogenes”. 5. Front Cell Infect Microbiol. 2014 Sep 30;4:135. doi: 10.3389/fcimb.2014.00135.

eCollection 2014.


PMCID: PMC3924034  PMID: 24592357

Guariglia-Oropeza V(1), Orsi RH(1), Yu H(2), Boor KJ(1), Wiedmann M(1), Guldimann C(1).   “Regulatory network features in Listeria monocytogenes-changing the way we talk”. 6. Front Cell Infect Microbiol. 2014 Feb 14;4:14. doi: 10.3389/fcimb.2014.00014.

eCollection 2014.


PMCID: PMC3920067  PMID: 24575393

D’Orazio SE(1). ”Animal models for oral transmission of Listeria monocytogenes”. 7. Front Cell Infect Microbiol. 2014 Feb 11;4:15. doi: 10.3389/fcimb.2014.00015. eCollection 2014.


PMCID: PMC3921577  PMID: 24575392

Cahoon LA(1), Freitag NE(1). “Listeria monocytogenes virulence factor secretion: don’t leave the cell without a Chaperone”.   8. Front Cell Infect Microbiol. 2014 Feb 12;4:13. doi: 10.3389/fcimb.2014.00013.eCollection 2014.


PMCID: PMC3913888  PMID: 24551601

Gahan CG(1), Hill C(2).“Listeria monocytogenes: survival and adaptation in the gastrointestinal tract”.  9. Front Cell Infect Microbiol. 2014 Feb 5;4:9. doi: 10.3389/fcimb.2014.00009. eCollection 2014.


PMCID: PMC4008456   PMID: 24800178 

Pol J(1), Bloy N(1), Obrist F(1), Eggermont A(2), Galon J(3), Hervé Fridman W(4), Cremer I(4), Zitvogel L(5), Kroemer G(6), Galluzzi L(7).

“Trial Watch: DNA vaccines for cancer therapy”. 10. Oncoimmunology. 2014 Jan 1;3(1):e28185. Epub 2014 Apr 1.


PMID: 24018504

Carrillo-Esper R(1), Carrillo-Cordova LD, Espinoza de los Monteros-Estrada I, Rosales-Gutiérrez AO, Uribe M, Méndez-Sánchez N.   “Rhombencephalitis by Listeria monocytogenes in a cirrhotic patient: a case report and literature review”.  11. Ann Hepatol. 2013 Sep-Oct;12(5):830-3.


PMCID: PMC3708349 PMID: 23698167

Harrison LM(1), Balan KV, Babu US. “Dietary fatty acids and immune response to food-borne bacterial infections”.  12. Nutrients. 2013 May 22;5(5):1801-22. doi: 10.3390/nu5051801.


PMCID: PMC3899140 PMID: 23399758

Sun R(1), Liu Y. “Listeriolysin O as a strong immunogenic molecule for the development of new anti-tumor vaccines”. 13. Hum Vaccin Immunother. 2013 May;9(5):1058-68. doi: 10.4161/hv.23871. Epub 2013 Feb 11.



PMCID: PMC3638699  PMID: 23653659

Sherrid AM(1), Kollmann TR. “Age-dependent differences in systemic and cell-autonomous immunity to L. Monocytogenes”. 14. Clin Dev Immunol. 2013;2013:917198. doi: 10.1155/2013/917198. Epub 2013 Apr 7.


PMCID: PMC3543101 PMID: 23125201

Pizarro-Cerdá J(1), Kühbacher A, Cossart P.” Entry of Listeria monocytogenes in mammalian epithelial cells: an updated view”. Cold Spring Harb Perspect Med. 2012 Nov 1;2(11). pii: a010009. doi: 10.1101/cshperspect.a010009.

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