Increased membrane surface positive charge and altered membrane fluidity leads to cationic antimicrobial peptide resistance in Enterococcus faecalis

ABSTRACTClostridium difficilecauses chronic intestinal disease, yet little is understood about how the bacterium interacts with and survives in the host. To colonize the intestine and cause persistent disease, the bacterium must circumvent killing by host innate immune factors, such as cationic antimicrobial peptides (CAMPs). In this study, we investigated the effect of model CAMPs on growth and found thatC. difficileis not only sensitive to these compounds but also responds to low levels of CAMPs by expressing genes that lead to CAMP resistance. By plating the bacterium on medium containing the CAMP nisin, we isolated a mutant capable of growing in three times the inhibitory concentration of CAMPs. This mutant also showed increased resistance to the CAMPs gallidermin and polymyxin B, demonstrating tolerance to different types of antimicrobial peptides. We identified the mutated gene responsible for the resistance phenotype as CD1352. This gene encodes a putative orphan histidine kinase that lies adjacent to a predicted ABC transporter operon (CD1349 to CD1351). Transcriptional analysis of the ABC transporter genes revealed that this operon was upregulated in the presence of nisin in wild-type cells and was more highly expressed in the CD1352 mutant. The insertional disruption of the CD1349 gene resulted in significant decreases in resistance to the CAMPs nisin and gallidermin but not polymyxin B. Because of their role in cationic antimicrobial peptide resistance, we propose the designationcprABCfor genes CD1349 to CD1351 andcprKfor the CD1352 gene. These results provide the first evidence of aC. difficilegene associated with antimicrobial peptide resistance.

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Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/j.bbamem.2015.02.010 ◽

2015 ◽

Vol 1848 (11) ◽

pp. 3047-3054 ◽

Cited By ~ 47

Author(s):

Christopher N. LaRock ◽

Victor Nizet

Keyword(s):

Antimicrobial Peptide ◽

Resistance Mechanisms ◽

Cationic Antimicrobial Peptide ◽

Antimicrobial Peptide Resistance

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Inactivation of the gene encoding the cationic antimicrobial peptide resistance factor MprF increases biofilm formation but reduces invasiveness of Listeria monocytogenes

Journal of Applied Microbiology ◽

10.1111/jam.14790 ◽

2020 ◽

Author(s):

J. Nowak ◽

S.B. Visnovsky ◽

C.D. Cruz ◽

G.C. Fletcher ◽

A.H.M. Vliet ◽

...

Keyword(s):

Listeria Monocytogenes ◽

Antimicrobial Peptide ◽

Biofilm Formation ◽

Resistance Factor ◽

Gene Encoding ◽

Cationic Antimicrobial Peptide ◽

Antimicrobial Peptide Resistance

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Potential Antimicrobial Peptides Elucidation From The Marine Bacteria

Cardiovascular & Hematological Agents in Medicinal Chemistry ◽

10.2174/1871525718666200512074400 ◽

2020 ◽

Vol 18 ◽

Cited By ~ 1

Author(s):

Adyasa Barik ◽

Pandiyan Rajesh ◽

Manthiram Malathi ◽

Vellaisamy Balasubramanian

Keyword(s):

Antimicrobial Peptide ◽

Marine Bacteria ◽

Unnatural Amino Acids ◽

Wide Spectrum ◽

Drug Resistant ◽

Medical Field ◽

The World ◽

Pathogenic Microbes ◽

Antimicrobial Peptide Resistance ◽

Significant Attention

: In recent years, over use of antibiotics has been raising its head to a serious problem all around the world as pathogens become drug resistant and create challenges to the medical field. This failure of most potent antibiotics that kill pathogens increases the thirst for research to look further way of killing pathogens. It has been led to the findings of antimicrobial peptide which is the most potent peptide to destroy pathogens. This review gives special emphasis to the usage of marine bacteria and other microorganisms for antimicrobial peptide (AMP) which are eco friendly as well as a developing class of natural and synthetic peptides with a wide spectrum of targets to pathogenic microbes. Consequently, a significant attention has been paid mainly to (i) the structure and types of anti microbial peptides and (ii) mode of action and mechanism of antimicrobial peptide resistance to pathogens. In addition to this, the designing of AMPs has been analysed thoroughly for reducing toxicity and developing better potent AMP. It has been done by the modified unnatural amino acids by amidation to target the control of biofilm and persister cell.

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Gene May Regulate Both Antimicrobial Peptide Resistance and Virulence

Microbe Magazine ◽

10.1128/microbe.3.475.2 ◽

2008 ◽

Vol 3 (10) ◽

pp. 475-475

Keyword(s):

Antimicrobial Peptide ◽

Antimicrobial Peptide Resistance

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Highly efficient nanomedicine from cationic antimicrobial peptide-protected Ag nanoclusters

Journal of Materials Chemistry B ◽

10.1039/d0tb02267e ◽

2021 ◽

Author(s):

Zhikai Ye ◽

Haishuang Zhu ◽

Shan Zhang ◽

Jing Li ◽

Jin Wang ◽

...

Keyword(s):

Antimicrobial Peptide ◽

Biological Systems ◽

Cationic Antimicrobial Peptide ◽

Highly Efficient ◽

Antimicrobial Efficiency ◽

Ag Nanoclusters ◽

Fine Tune

Designing the homogeneous assembly of the bio–nano interface to fine-tune the interactions between the nanoprobes and biological systems is of prime importance to improve the antimicrobial efficiency of nanomedicines.

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Insights into the Action Mechanism of the Antimicrobial Peptide Lasioglossin III

International Journal of Molecular Sciences ◽

10.3390/ijms22062857 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2857

Author(s):

Filomena Battista ◽

Rosario Oliva ◽

Pompea Del Vecchio ◽

Roland Winter ◽

Luigi Petraccone

Keyword(s):

Antimicrobial Peptide ◽

Gram Negative Bacteria ◽

Lipid Domains ◽

Action Mechanism ◽

Cationic Antimicrobial Peptide ◽

Intracellular Targeting ◽

Gel Retardation Assay ◽

Charged Membrane ◽

Intracellular Target ◽

Anionic Lipids

Lasioglossin III (LL-III) is a cationic antimicrobial peptide derived from the venom of the eusocial bee Lasioglossum laticeps. LL-III is extremely toxic to both Gram-positive and Gram-negative bacteria, and it exhibits antifungal as well as antitumor activity. Moreover, it shows low hemolytic activity, and it has almost no toxic effects on eukaryotic cells. However, the molecular basis of the LL-III mechanism of action is still unclear. In this study, we characterized by means of calorimetric (DSC) and spectroscopic (CD, fluorescence) techniques its interaction with liposomes composed of a mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-rac-phosphoglycerol (POPG) lipids as a model of the negatively charged membrane of pathogens. For comparison, the interaction of LL-III with the uncharged POPC liposomes was also studied. Our data showed that LL-III preferentially interacted with anionic lipids in the POPC/POPG liposomes and induces the formation of lipid domains. Furthermore, the leakage experiments showed that the peptide could permeabilize the membrane. Interestingly, our DSC results showed that the peptide-membrane interaction occurs in a non-disruptive manner, indicating an intracellular targeting mode of action for this peptide. Consistent with this hypothesis, our gel-retardation assay experiments showed that LL-III could interact with plasmid DNA, suggesting a possible intracellular target.

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