Renoprotective effect of Limonium duriusculum (de Girard) Kuntze via modulation of oxidative stress/ UPR markers and inflammation during cyclosporine-induced nephrotoxicity in rats.

Objectives: The present study aimed to explore the mechanisms underlying the potency of the renoprotective effect of the EtOAc fraction of Limonium duriusculum (EALD) (Plumbaginaceae) against cyclosporine A (CsA), in comparison to vitamin E (Vit. E). Materials and Methods: In the in-vivo experiment, a model of CsA-induced nephrotoxicity was established by dosing male Wistar rats with 25 mg/kg, for 14 days. The protective effect of EALD was investigated through pretreatment of rats with a dose of 200 mg/kg for 14 days, compared to the oral administration of Vit. E at 100 mg/kg. Renal function and markers of oxidative stress were then assessed. Furthermore, a complementary in-vitro study was carried out to evaluate CsA-induced endoplasmic reticulum stress (ERS) and inflammation on cell culture (3T3 cells and MCT cells) using western blot and quantitative RT-PCR.. Results: Pretreatment of rats with EALD significantly attenuated the elevated levels of renal dysfunction markers (BUN, creatinine) and suppressed malondialdehyde (MDA) levels; It also significantly regulated the changes in superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxydase (GPx), and glutathione S-transferase (GST) levels as compared to Vit. E, demonstrating a more effective recovery in renal tissues. Treatment of cells with CsA was linked to the expression of ERS and inflammatory markers activating transcription factor (ATF4), inositol-requiring enzyme 1α (IRE1α), binding immunoglobulin protein (BiP), and monocyte chemoattractant protein-1 (MCP1). In contrast, pretreatment of cells with EALD resulted in a significant decrease in both ERS and inflammatory markers. Conclusion: These findings indicate the renoprotective potential of L. duriusculum, as it demonstrated the ability to ameliorate CsA-induced renal dysfunction through its distinctive antioxidant properties.

Regulated necrosis role in inflammation and repair in acute kidney injury.

Acute kidney injury (AKI) frequently occurs in patients with chronic kidney disease (CKD) and in turn, may cause or accelerate CKD. Therapeutic options in AKI are limited and mostly relate to replacement of kidney function until the kidneys recover spontaneously. Furthermore, there is no treatment that prevents the AKI-to-CKD transition. Regulated necrosis has recently emerged as key player in kidney injury. Specifically, there is functional evidence for a role of necroptosis, ferroptosis or pyroptosis in AKI and the AKI-to-CKD progression. Regulated necrosis may be proinflammatory and immunogenic, triggering subsequent waves of regulated necrosis. In a paradigmatic murine nephrotoxic AKI model, a first wave of ferroptosis was followed by recruitment of inflammatory cytokines such as TWEAK that, in turn, triggered a secondary wave of necroptosis which led to persistent kidney injury and decreased kidney function. A correct understanding of the specific forms of regulated necrosis, their timing and intracellular molecular pathways may help design novel therapeutic strategies to prevent or treat AKI at different stages of the condition, thus improving patient survival and the AKI-to-CKD transition. We now review key regulated necrosis pathways and their role in AKI and the AKI-to-CKD transition both at the time of the initial insult and during the repair phase following AKI.

BET Protein Inhibitor JQ1 Ameliorates Experimental Peritoneal Damage by Inhibition of Inflammation and Oxidative Stress.

Peritoneal dialysis (PD) is a current replacement therapy for end-stage kidney diseases (ESKDs). However, long-term exposure to PD fluids may lead to damage of the peritoneal membrane (PM) through mechanisms involving the activation of the inflammatory response and mesothelial-to-mesenchymal transition (MMT), leading to filtration failure. Peritoneal damage depends on a complex interaction among external stimuli, intrinsic properties of the PM, and subsequent activities of the local innate-adaptive immune system. Epigenetic drugs targeting bromodomain and extra-terminal domain (BET) proteins have shown beneficial effects on different experimental preclinical diseases, mainly by inhibiting proliferative and inflammatory responses. However the effect of BET inhibition on peritoneal damage has not been studied. To this aim, we have evaluated the effects of treatment with the BET inhibitor JQ1 in a mouse model of peritoneal damage induced by chlorhexidine gluconate (CHX). We found that JQ1 ameliorated the CHX-induced PM thickness and inflammatory cell infiltration. Moreover, JQ1 decreased gene overexpression of proinflammatory and profibrotic markers, together with an inhibition of the nuclear factor-κB (NF-κB) pathway. Additionally, JQ1 blocked the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and restored changes in the mRNA expression levels of NADPH oxidases (NOX1 and NOX4) and NRF2/target antioxidant response genes. To corroborate the in vivo findings, we evaluated the effects of the BET inhibitor JQ1 on PD patients' effluent-derived primary mesothelial cells and on the MeT-5A cell line. JQ1 inhibited tumor necrosis factor-α (TNF-α)-induced proinflammatory gene upregulation and restored MMT phenotype changes, together with the downmodulation of oxidative stress. Taken together, these results suggest that BET inhibitors may be a potential therapeutic option to ameliorate peritoneal damage.

STING1 deficiency ameliorates immune-mediated crescentic glomerulonephritis in mice.

Rapidly progressive/crescentic glomerulonephritis (RPGN/CGN) involves the formation of glomerular crescents by maladaptive differentiation of parietal epithelial cells that leads to rapid loss of renal function. The molecular mechanisms of crescent formation are poorly understood. Therefore, new insights into molecular mechanisms could identify alternative therapeutic targets for RPGN/CGN. Analysis of kidney biopsies from patients with RPGN revealed increased interstitial, glomerular, and tubular expression of STING1, an accessory protein of the c-GAS-dependent DNA-sensing pathway, which was also observed in murine nephrotoxic nephritis induced by an anti-GBM antibody. STING1 was expressed by key cell types involved in RPGN and crescent formation such as glomerular parietal epithelial cells, and tubular cells as well as by inflammation accessory cells. In functional in vivo studies, Sting1-/- mice with nephrotoxic nephritis had lower kidney cytokine expression, milder kidney infiltration by innate and adaptive immune cells, and decreased disease severity. Pharmacological STING1 inhibition mirrored these findings. Direct STING1 agonism in parietal and tubular cells activated the NF-κB-dependent cytokine response and the interferon-induced genes (ISGs) program. These responses were also triggered in a STING1-dependent manner by the pro-inflammatory cytokine TWEAK. These results identify STING1 activation as a pathological mechanism in RPGN/CGN and TWEAK as an activator of STING1. Pharmacological strategies targeting STING1, or upstream regulators may therefore be potential alternatives to treat RPGN. © 2023 The Pathological Society of Great Britain and Ireland.

Mitochondrial Dysfunction in the Cardio-Renal Axis.

Cardiovascular disease (CVD) frequently complicates chronic kidney disease (CKD). The risk of all-cause mortality increases from 20% to 500% in patients who suffer both conditions; this is referred to as the so-called cardio-renal syndrome (CRS). Preclinical studies have described the key role of mitochondrial dysfunction in cardiovascular and renal diseases, suggesting that maintaining mitochondrial homeostasis is a promising therapeutic strategy for CRS. In this review, we explore the malfunction of mitochondrial homeostasis (mitochondrial biogenesis, dynamics, oxidative stress, and mitophagy) and how it contributes to the development and progression of the main vascular pathologies that could be affected by kidney injury and vice versa, and how this knowledge may guide the development of novel therapeutic strategies in CRS.

Regulated cell death pathways in kidney disease.

Disorders of cell number that result from an imbalance between the death of parenchymal cells and the proliferation or recruitment of maladaptive cells contributes to the pathogenesis of kidney disease. Acute kidney injury can result from an acute loss of kidney epithelial cells. In chronic kidney disease, loss of kidney epithelial cells leads to glomerulosclerosis and tubular atrophy, whereas interstitial inflammation and fibrosis result from an excess of leukocytes and myofibroblasts. Other conditions, such as acquired cystic disease and kidney cancer, are characterized by excess numbers of cyst wall and malignant cells, respectively. Cell death modalities act to clear unwanted cells, but disproportionate responses can contribute to the detrimental loss of kidney cells. Indeed, pathways of regulated cell death - including apoptosis and necrosis - have emerged as central events in the pathogenesis of various kidney diseases that may be amenable to therapeutic intervention. Modes of regulated necrosis, such as ferroptosis, necroptosis and pyroptosis may cause kidney injury directly or through the recruitment of immune cells and stimulation of inflammatory responses. Importantly, multiple layers of interconnections exist between different modalities of regulated cell death, including shared triggers, molecular components and protective mechanisms.

"Blueberry muffin": Manifestación atípica de una infección congénita frecuente / Blueberry muffin baby: an atypical manifestation of a common congenital infection

El síndrome "blueberry muffin" es una dermatosis maculopapular eritematoviolácea como resultado de una hematopoyesis extramedular. Se ha asociado con infecciones del espectro TORCH y causas no infecciosas. Presentamos el caso de un recién nacido pretérmino, quien desde el control prenatal presentó una ecografía con signos sugerentes de infección congénita por citomegalovirus (microcefalia, ventriculomegalia y calcificaciones intracerebrales). Al examen físico presentaba una dermatosis macular violácea compatible con síndrome "blueberry muffin". Se detectó carga viral de citomegalovirus en orina (81,200 copias/ml) e inició tratamiento con ganciclovir, con desenlace fatal. La infección congénita por CMV debe considerarse ante el síndrome "blueberry muffin"; el adecuado abordaje diagnóstico debe ser oportuno y debe incluir antecedentes maternos y perinatales, así como estudios serológicos para infecciones por TORCH con el fin del inicio precoz de tratamiento para evitar complicaciones y secuelas.

Blueberry muffin syndrome is characterized by an erythematousviolaceous maculopapular dermatosis due to extramedullary hematopoiesis. This entity has been associated with TORCH spectrum infections and noninfectious causes. We present the case of a preterm newborn, who since the prenatal control gave an ultrasound with data suggestive of congenital infection by cytomegalovirus (microcephaly, ventriculomegaly, intracerebral calcifications). On physical examination, he presented a violaceous macular dermatosis compatible with blueberry muffin syndrome. Cytomegalovirus viral load was detected in urine (81,200 copies/ml), with fatal outcome. Congenital cytomegalovirus infection should be considered in the presence of a blueberry muffin syndrome; an adequate diagnostic approach that includes maternal and perinatal history is essential, as well as serology studies for diseases of the TORCH spectrum in order to start early with treatment and avoid major comorbidities.

Advances in Characterizing the Transport Systems of and Resistance to EntDD14, A Leaderless Two-Peptide Bacteriocin with Potent Inhibitory Activity.

Enterocin DD14 (EntDD14) is a two-peptide leaderless bacteriocin produced by the Enterococcus faecalis 14 strain previously isolated from meconium. This bacteriocin is mainly active against Gram-positive bacteria. Leaderless bacteriocins do not undergo post-translational modifications and are therefore immediately active after their synthesis. As a result, the cells that produce such bacteriocins have developed means of protection against them which often involve transport systems. In this and our previous work, we constructed different mutants deleted in the genes involved in the transport functions, thus covering all the supposed components of this transport system, using Listeria innocua ATCC 33090 as the indicator strain to assess the activity of externalized EntDD14. We also assessed the self-resistance of the WT and all its engineered derivative mutants against EntDD14, provided extracellularly, in order to evaluate their self-resistance. The results obtained highlight that the ABC transporter constituted by the DdG, H, I, and J proteins contributes to EntDD14 export as well as resistance to an external supply of EntDD14. Our results also have established the essential role of the DdE and DdF proteins as primary transporters dedicated to the externalization of EntDD14. Moreover, the in silico data showed that DdE and DdF appear to assemble in a formation that forms an essential channel for the exit of EntDD14. This channel DdEF may interact with the ABC transporter DdGHIJ in order to control the flow of bacteriocin across the membrane, although the nature of this interaction remains to be elucidated.

Phonon-mediated room-temperature quantum Hall transport in graphene.

The quantum Hall (QH) effect in two-dimensional electron systems (2DESs) is conventionally observed at liquid-helium temperatures, where lattice vibrations are strongly suppressed and bulk carrier scattering is dominated by disorder. However, due to large Landau level (LL) separation (~2000 K at B = 30 T), graphene can support the QH effect up to room temperature (RT), concomitant with a non-negligible population of acoustic phonons with a wave-vector commensurate to the inverse electronic magnetic length. Here, we demonstrate that graphene encapsulated in hexagonal boron nitride (hBN) realizes a novel transport regime, where dissipation in the QH phase is governed predominantly by electron-phonon scattering. Investigating thermally-activated transport at filling factor 2 up to RT in an ensemble of back-gated devices, we show that the high B-field behaviour correlates with their zero B-field transport mobility. By this means, we extend the well-accepted notion of phonon-limited resistivity in ultra-clean graphene to a hitherto unexplored high-field realm.

An approach to robust condition monitoring in industrial processes using pythagorean membership grades.

In this paper, a robust approach to improve the performance of a condition monitoring process in industrial plants by using Pythagorean membership grades is presented. The FCM algorithm is modified by using Pythagorean fuzzy sets, to obtain a new variant of it called Pythagorean Fuzzy C-Means (PyFCM). In addition, a kernel version of PyFCM (KPyFCM) is obtained in order to achieve greater separability among classes, and reduce classification errors. The approach proposed is validated using experimental datasets and the Tennessee Eastman (TE) process benchmark. The results are compared with the results obtained with other algorithms that use standard and non-standard membership grades. The highest performance obtained by the approach proposed indicate its feasibility.

Gain-of-function TLR7 and loss-of-function A20 gene variants identify a novel pathway for Mendelian lupus and lupus nephritis.

Systemic lupus erythematosus (SLE) is a chronic and inflammatory autoimmune disease of unknown origin that may cause kidney disease, i.e. lupus nephritis (LN). Within a wider trend towards an expanding field of genetic causes of kidney disease, two recent reports have emphasized the role of Mendelian autoimmune disorders in causing LN both in children and in young adults. Loss-of-function (LOF) variants of tumor necrosis factor alpha-induced protein 3 (TNFAIP3) and gain of function (GOF) variants of Toll-like receptor 7 (TLR7) cause SLE and LN, respectively. Interestingly, both genes regulate the same signaling route, as A20, the protein encoded by TNFAIP3, inhibits nuclear factor ĸB (NF-ĸB) activation while TLR7 promoted NF-ĸB activation. Moreover, TNFAIP3 and TLR7 variants are relatively frequent, potentially contributing to polygenic risk for LN. Finally, they both may be expressed by kidney cells, potentially contributing to the severity of kidney injury in persons who have already developed autoimmunity. The fact that both genes regulate the same pathway may lead to novel therapeutic approaches targeting the shared molecular pathway.

Crosstalk between TBK1/IKKε and the type I interferon pathway contributes to tubulointerstitial inflammation and kidney tubular injury.

The type I interferon (TI-IFN) pathway regulates innate immunity, inflammation, and apoptosis during infection. However, the contribution of the TI-IFN pathway or upstream signaling pathways to tubular injury in kidney disease is poorly understood. Upon observing evidence of activation of upstream regulators of the TI-IFN pathway in a transcriptomics analysis of murine kidney tubulointerstitial injury, we have now addressed the impact of the TI-IFN and upstream signaling pathways on kidney tubulointerstitial injury. In cultured tubular cells and kidney tissue, IFNα/ß binding to IFNAR activated the TI-IFN pathway and recruited antiviral interferon-stimulated genes (ISG) and NF-κB-associated proinflammatory responses. TWEAK and lipopolysaccharide (LPS) signaled through TBK1/IKKε and IRF3 to activate both ISGs and NF-κB. In addition, TWEAK recruited TLR4 to stimulate TBK1/IKKε-dependent ISG and inflammatory responses. Dual pharmacological inhibition of TBK1/IKKε with amlexanox decreased TWEAK- or LPS-induced ISG and cytokine responses, as well as cell death induced by a complex inflammatory milieu that included TWEAK. TBK1 or IRF3 siRNA prevented the TWEAK-induced ISG and inflammatory gene expression while IKKε siRNA did not. In vivo, kidney IFNAR and IFNß were increased in murine LPS and folic acid nephrotoxicity while IFNAR was increased in human kidney biopsies with tubulointerstitial damage. Inhibition of TBK1/IKKε with amlexanox or IFNAR neutralization decreased TI-IFN pathway activation and protected from kidney injury induced by folic acid or LPS. In conclusion, TI-IFNs, TWEAK, and LPS engage interrelated proinflammatory and antiviral responses in tubular cells. Moreover, inhibition of TBK1/IKKε with amlexanox, and IFNAR targeting, may protect from tubulointerstitial kidney injury.

Tubular Mitochondrial Dysfunction, Oxidative Stress, and Progression of Chronic Kidney Disease.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are interconnected conditions, and CKD is projected to become the fifth leading global cause of death by 2040. New therapeutic approaches are needed. Mitochondrial dysfunction and oxidative stress have emerged as drivers of kidney injury in acute and chronic settings, promoting the AKI-to-CKD transition. In this work, we review the role of mitochondrial dysfunction and oxidative stress in AKI and CKD progression and discuss novel therapeutic approaches. Specifically, evidence for mitochondrial dysfunction in diverse models of AKI (nephrotoxicity, cytokine storm, and ischemia-reperfusion injury) and CKD (diabetic kidney disease, glomerulopathies) is discussed; the clinical implications of novel information on the key role of mitochondria-related transcriptional regulators peroxisome proliferator-activated receptor gamma coactivator 1-alpha, transcription factor EB (PGC-1α, TFEB), and carnitine palmitoyl-transferase 1A (CPT1A) in kidney disease are addressed; the current status of the clinical development of therapeutic approaches targeting mitochondria are updated; and barriers to the clinical development of mitochondria-targeted interventions are discussed, including the lack of clinical diagnostic tests that allow us to categorize the baseline renal mitochondrial dysfunction/mitochondrial oxidative stress and to monitor its response to therapeutic intervention. Finally, key milestones for further research are proposed.

Impact of ketamine versus fentanyl continuous infusion on opioid use in patients admitted to a surgical-trauma intensive care unit.

OBJECTIVE: Ketamine has been shown to decrease opioid utilization as an adjunct, but limited evidence is available on ketamine as a primary analgesic strategy. DESIGN: A retrospective chart review. PATIENTS AND PARTICIPANTS: Mechanically ventilated adult patients (≥18 years) in the surgery-trauma intensive care unit (STICU) with continuous infusion ketamine or fentanyl with concomitant propofol for at least 12 hours were screened for inclusion. The final analysis included 22 patients in the ketamine/propofol (KP) group and 24 patients in the fentanyl/propofol (FP) group. INTERVENTIONS: Patients in the STICU received KP or FP continuous infusions. MAIN OUTCOME MEASURES: The primary outcome compared opioid requirements between both groups during mechanical ventilation. RESULTS: The median opioid requirement during mechanical ventilation was significantly higher in the FP group compared to the KP group (median 1,392 milligrams of morphine equivalents (MMEs) [interquartile range (IQR) 709.5-2,292] versus 206.3 MME [IQR 87-510], p < 0.001). After extubation, there was no difference in opioid utilization. Patients in the KP group spent less time at goal Critical Care Pain Observation Tool compared to the FP group (median 77.6 percent, IQR [71.9-85.2] versus 88.9 percent, IQR [76.9-97.4], p = 0.003). The proportions of patients developing adverse effects were not significantly different between the two groups. CONCLUSIONS: Among critically ill mechanically ventilated patients in the STICU, continuous ketamine resulted in signifi-cantly less opioids during mechanical ventilation. Further studies with a larger sample size are needed to assess the ap-propriate dosing strategy for ketamine to produce adequate analgesia when used as a primary analgesic in mechanically ventilated patients.

Anti-adhesion and Anti-inflammatory Potential of the Leaderless Class IIb Bacteriocin Enterocin DD14.

In this study, we investigate the interactions between the leaderless class IIb bacteriocin, enterocin DD14 (EntDD14), or the methicillin or the combination of these antibacterials, and two methicillin-resistant Staphylococcus aureus strains (MRSA-S1 and USA 300) which are respectively a clinical strain and a reference strain. The results obtained showed that EntDD14 alone or in combination with the antibiotic could significantly prevent the adhesion of these pathogenic bacteria to human cells. On the other hand, we investigated the anti-inflammatory effect of EntDD14 on the secretion of pro-inflammatory interleukins, including IL-6 and IL-8. The results show that EntDD14 is able to decrease significantly the secretion of both interleukins on Caco-2 cells following their treatments with lipopolysaccharides. These novel data provide insightful informations to support applications of bacteriocins as therapeutic agents capable as well to defeat pathogenic bacteria and concomitantly limit their inflammatory reactions.

Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney.

Chronic kidney disease (CKD) can be considered as a clinical model for premature aging. However, non-invasive biomarkers to detect early kidney damage and the onset of a senescent phenotype are lacking. Most of the preclinical senescence studies in aging have been done in very old mice. Furthermore, the precise characterization and over-time development of age-related senescence in the kidney remain unclear. To address these limitations, the age-related activation of cellular senescence-associated mechanisms and their correlation with early structural changes in the kidney were investigated in 3- to 18-month-old C57BL6 mice. Inflammatory cell infiltration was observed by 12 months, whereas tubular damage and collagen accumulation occurred later. Early activation of cellular-senescence-associated mechanisms was found in 12-month-old mice, characterized by activation of the DNA-damage-response (DDR), mainly in tubular cells; activation of the antioxidant NRF2 pathway; and klotho downregulation. However, induction of tubular-cell-cycle-arrest (CCA) and overexpression of renal senescent-associated secretory phenotype (SASP) components was only found in 18-month-old mice. In aging mice, both inflammation and oxidative stress (marked by elevated lipid peroxidation and NRF2 inactivation) remained increased. These findings support the hypothesis that prolonged DDR and CCA, loss of nephroprotective factors (klotho), and dysfunctional redox regulatory mechanisms (NRF2/antioxidant defense) can be early drivers of age-related kidney-damage progression.

Evidence for the Involvement of Pleckstrin Homology Domain-Containing Proteins in the Transport of Enterocin DD14 (EntDD14); a Leaderless Two-Peptide Bacteriocin.

Bacteriocins synthesis is initiated from an inactive precursor, which is composed of an N-terminal leader peptide attached to a C-terminal pro-peptide. However, leaderless bacteriocins (LLB) do not possess this N-terminal leader peptide nor undergo post-translational modifications. These atypical bacteriocins are observed to be immediately active after their translation in the cytoplasm. However, although considered to be simple, the biosynthetic pathway of LLB remains to be fully understood. Enterocin DD14 (EntDD14) is a two-peptide LLB produced by Enterococcus faecalis 14, which is a strain isolated from meconium. In silico analysis of DNA encoding EntDD14 located a cluster of 10 genes ddABCDEFGHIJ, where ddE and ddF encode the peculiar DdE and DdF proteins, carrying pleckstrin homology (PH) domains. These modules are quite common in Eucarya proteins and are known to be involved in intracellular signaling or cytoskeleton organization. To elucidate their role within the EntDD14 genetic determinants, we constructed deletion mutants of the ddE and ddF genes. As a result, the mutants were unable to export EntDD14 outside of the cytoplasm even though there was a clear expression of structural genes ddAB encoding EntDD14, and genes ddHIJ encoding an ABC transporter. Importantly, in these mutant strains (ΔddE and ΔddF), EntDD14 was detected by mass spectrometry in the intracellular soluble fraction exerting, upon its accumulation, a toxic effect on the producing strain as revealed by cell-counting and confocal microscopy analysis. Taken together, these results clearly indicate that PH domain-containing proteins, such as DdE and DdF, are involved in the transport of the leaderless two-peptide EntDD14.

Current Knowledge of the Mode of Action and Immunity Mechanisms of LAB-Bacteriocins.

Bacteriocins produced by lactic acid bacteria (LAB-bacteriocins) may serve as alternatives for aging antibiotics. LAB-bacteriocins can be used alone, or in some cases as potentiating agents to treat bacterial infections. This approach could meet the different calls and politics, which aim to reduce the use of traditional antibiotics and develop novel therapeutic options. Considering the clinical applications of LAB-bacteriocins as a reasonable and desirable therapeutic approach, it is therefore important to assess the advances achieved in understanding their modes of action, and the resistance mechanisms developed by the producing bacteria to their own bacteriocins. Most LAB-bacteriocins act by disturbing the cytoplasmic membrane through forming pores, or by cell wall degradation. Nevertheless, some of these peptides still have unknown modes of action, especially those that are active against Gram-negative bacteria. Regarding immunity, most bacteriocin-producing strains have an immunity mechanism involving an immunity protein and a dedicated ABC transporter system. However, these immunity mechanisms vary from one bacteriocin to another.