The multifunctional promyelocytic leukemia protein (PML) is involved in the regulation of various cellular processes in both physiological and pathological conditions. Specifically, PML is one of the inositol-1,4,5-trisphosphate receptors (IPRs) activity regulators and can influence Ca transport from the endoplasmic reticulum (ER) to mitochondria. In this work, the effects of PML knockout on calcium homeostasis in the cytosol, ER, and mitochondria of HeLa cells were studied upon stimulation with histamine, which induces Ca mobilization from the ER via IPRs. We utilized calcium indicators with different subcellular localizations, including synthetic dyes Fura-2 (cytosolic), Xrhod-5F (mitochondrial), and protein sensor R-CEPIAer (ER), as well as mitochondrial potential-sensitive probes Rh123 and TMRM. Our results show that PML knockout induced changes in HeLa cell and mitochondrial morphology, slightly decreased basal and integral Ca levels, enhanced mitochondrial Ca uptake from the cytoplasm, and maintained residual mitochondrial potential after depolarization. Additionally, it reduced the Ca pool in ER membranes not associated with histamine receptor activation and, consequently, IPRs. These findings suggest that changes in calcium ion transport due to PML knockout in HeLa cells affect mitochondrial activity.

Pretreatment of Physcomitrium patens with abscisic acid (ABA) has been shown to induce desiccation tolerance. While previous research suggests that ABA-induced production of proteins and soluble sugars contributes to desiccation stress tolerance, additional mechanisms underlying this tolerance remain unclear. In this study, we found that ABA pretreatment led to increased levels of digalactosyl diacylglycerol (DGDG), phosphatidylcholine (PC), and phosphatidylinositol (PI), along with a decrease in monogalactosyl diacylglycerol (MGDG). These changes elevated the MGDG/DGDG and PC/phosphatidylethanolamine (PE) ratios, potentially stabilizing membranes and enhancing desiccation tolerance. Furthermore, ABA pretreatment effectively prevented membrane lipid degradation during desiccation and subsequent rehydration. These findings highlight ABA's role in desiccation tolerance through membrane lipid modulation, providing new insights into stress tolerance mechanisms in bryophytes.

Signal transducer and activator of transcription 3 (STAT3) is a multifactorial regulator involved in many biological responses. Alternative splicing of STAT3 pre-mRNA leads to an internal 50-nucleotide deletion of exon 23 selecting an alternative 3' acceptor site, resulting in the generation of two splicing isoforms, STAT3α and STAT3β. STAT3β lacks 55 amino acid-residue transactivation domain at the C-terminal of STAT3α replacing seven unique amino acids. Although STAT3β was originally thought to be a dominant negative isoform of STAT3α, accumulating evidence have shown that STAT3β possesses both its unique functions and those that overlap with STAT3α in fundamental cellular processes. However, much remains unknown about STAT3 pre-mRNA alternative splicing in determining the balance between STAT3 isoforms. In this study, we identified cis-regulatory elements and CUGBP2/ETR-3 as a novel trans-acting factor that regulates STAT3 alternative splicing. Our findings demonstrate that STAT3 splicing can be modulated by CUGBP2 via association with UG-rich elements of intron 22, providing a novel insight into the mechanism of STAT3 alternative splicing. CUGBP2 would be a crucial molecule regulating the balance of STAT3 isoform expression, thus targeting CUGBP2 and its recognition sequences in intron 22 of STAT3 might impact on various biological processes regulated by STAT3 signaling pathway.

Preeclampsia (PE) is a complex multi-organ disorder characterized by systemic inflammation, endothelial dysfunction, and vasoconstriction, which manifests as hypertension, with or without proteinuria. Effective preventive strategies for PE are currently lacking in clinical practice, leading to significant morbidity and mortality among mothers and newborns.

This study investigates the effects of microgravity on the differentiation and mineralization of IDG-SW3 osteocyte-like cells to understand the response of bone cells to microgravity and develop strategies to mitigate bone loss in astronauts. IDG-SW3 cells were cultured in collagen-coated dishes and subjected to a 3D clinostat to simulate microgravity 14 days after initiating differentiation. The static group remained under normal gravity. Cells were analyzed on days 14, 18, 22, and 26. Alizarin red staining demonstrated a substantial and time-dependent increase in mineralization in the static group, whereas the microgravity group exhibited little detectable mineralization throughout the experimental period. Quantitative RT-PCR revealed significant upregulation of Rankl, Alpl, Dmp1, and Fgf23 and downregulation of Sost and Phex in the microgravity group. RNA sequencing on day 26 showed distinct gene expression profiles between conditions. Heatmaps highlighted upregulated genes (Ptgs2, Alpl, Comp, Atf4, Lox) and downregulated genes (Rspo2, Ank, Ptn, Mmp13, Aspn, Spp1) under microgravity. Gene ontology (GO) enrichment analysis indicated that upregulated genes were associated with cytoskeletal organization and receptor activities, while downregulated genes were linked to extracellular matrix components and immune response. These findings provide insights into the molecular mechanisms of bone loss in space and emphasize the importance of gravity in bone remodeling. Future studies should validate these genes' functions in osteocyte biology under microgravity.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) serves as an adaptive immune system in bacteria and archaea, offering a defense mechanism against invading genetic elements such as viruses (bacteriophages) and plasmids. Today, CRISPR has evolved into a powerful gene-editing technology that enables highly specific and rapid modifications of DNA within a genome. It has a broad range of applications across various fields, including medicine, agriculture, and fundamental research. One of the significant challenges facing this technology is the efficient transfer of CRISPR constructs into target cells for gene editing. There are several methods to deliver this system into target cells, which can be classified as viral and non-viral methods. Each of these approaches has its own advantages and disadvantages. Recently, the use of extracellular vesicles for delivery has garnered particular attention. Exosomes are nano-sized extracellular vesicles that have emerged as promising carriers for drug delivery due to their unique properties. These naturally occurring vesicles, typically ranging from 30 to 150 nm in diameter, facilitate intercellular communication by transferring bioactive molecules such as proteins, lipids, and nucleic acids between cells. Exosome therapy has surfaced as a promising strategy in regenerative medicine, utilizing small extracellular vesicles to deliver therapeutic molecules to target cells. One of the emerging options for transferring the CRISPR system is exosomes. The integration of these two advanced technologies holds significant potential for developing efficient and targeted gene editing and advancing precision medicine. In contemporary medicine, there is an increasing focus on personalized and targeted treatments that cater to the distinct genetic and molecular profiles of individual patients. The synergy of CRISPR technology and exosome therapy presents a remarkable opportunity to develop highly targeted and effective therapeutic strategies customized to individual patient requirements. This review article examines the potential of incorporating CRISPR technology within exosomes for precision therapeutic applications.

Many pathogens establish a successful infection by evading the host complement system, an essential arm of innate immunity. Pathogenic Leptospira is reported to escape complement-mediated killing by recruiting the host complement regulators by lipoproteins or outer surface proteins. One of the outer surface proteins, Leptospiral complement regulator-acquiring protein A (LcpA), is known to recruit complement regulators, C4b-binding protein (C4BP), and Factor H (FH) on the bacterial surface. Mapping of interacting domains from C4BP and FH with the LcpA has already been reported. However, the region or structural part of the LcpA mediating the interaction is not known yet. Here, we report cloning, expression, refolding and purification of recombinant LcpA from an inclusion body of E. coli heterologous expression system. We also demonstrate the biophysical characterization of recombinant LcpA and reveal its secondary structure contents. Moreover, the protein displays a moderate thermostability. The change of intrinsic fluorescence and CD spectra demonstrate a change in the secondary structure of protein due to binding with Zn ions. Molecular docking of LcpA with the complement regulators displays important interface residues from both the individual counterparts. Molecular dynamic simulation analysis demonstrates the stability of interactions between LcpA and C4BP. In our understanding, this is the first report on the large-scale purification of LcpA through refolding experiments and biophysical characterization of LcpA. This study may provide additional information on the structural basis of binding with the complement regulators.

16S rRNA gene sequence is the most common housekeeping genetic marker to study bacterial phylogeny and taxonomy. Therefore, 16S rRNA gene sequencing has the potential to identify novel bacteria and diagnose bacteria. This study compared 16S rRNA gene sequencing with conventional PCR for bacterial identification and disease diagnosis. The bacterial community in healthy and diseased hosts was analyzed by 16S rRNA gene sequencing. 16S rRNA gene sequencing is more sensitive than conventional PCR in detecting bacteria. Moreover, 16S rRNA gene sequencing is adequate to identify novel bacteria. 16S rRNA gene sequencing demonstrated that most pathogenic bacteria persist in diseased or healthy hosts in different abundance. Pathogenic bacteria, such as well-known chicken pathogen Avibacterium paragallinarum, Ornithobacterium rhinotracheale, and Gallibacterium anatis, were identified as indicator species of diseased samples. Alpha diversity analysis showed that the healthy group species is significantly higher than in the diseased groups. Beta diversity analysis also demonstrated differences between healthy and infected groups. The study concluded that 16S rRNA gene sequencing is a more sensitive method for detecting pathogens, and microbiota analysis can distinguish between healthy and diseased samples. Eventually, 16S rRNA gene sequencing has represented the potential in human and animal clinical diagnosis and novel bacterial identification.

Isolated enzymes serve as advantageous platforms for the fabrication of nanomaterials. The objective of this study was to fabricate silver nanoparticles (AgNPs) incorporated with Trametes versicolor laccase and evaluate their diverse biological properties. The AgNPs fabricated through laccase-mediated methods were characterized using various characterization techniques including UV-visible (UV-vis) spectroscopy, Energy-dispersive X-ray (EDX) spectroscopy, Dynamic light scattering (DLS) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, and Field emission scanning electron microscopy (FE-SEM). The results showed that the laccase-incorporated AgNPs were spherical in shape with a Z-average diameter of 19.40 nm and a zeta potential of -19.2 mV. The AgNPs exhibited significant dose-dependent in vitro α-amylase, urease, and DPPH free radical inhibitory activities, with maximum inhibitions of 83.49 ± 1.06 %, 68.95 ± 3.60 %, and 67.36 ± 3.40 %, respectively, at a concentration of 1000 μg mL. Furthermore, the intrinsic pathway-mediated anticoagulant activity of the fabricated AgNPs was confirmed through the activated partial thromboplastin time (aPTT) assay, which serves as a global coagulation assay. Additionally, the laccase-incorporated AgNPs demonstrated antibacterial properties against both standard gram-positive strains of Staphylococcus epidermidis and Streptococcus mutans, with minimum inhibitory concentration (MIC) values of 2 and 4 μg mL, and minimum bactericidal concentration (MBC) values of 16 and 16 μg mL, respectively. The dose-dependent antibacterial performance of the AgNPs against both bacterial populations was also confirmed through flow cytometry. Moreover, the AgNPs exhibited 61.53 ± 3.17 % and 63.03 ± 1.44 % biofilm degradation against S. epidermidis and S. mutans, respectively, at the maximum tested concentration (20∗MIC).

Type 2 diabetes development has been associated with islet amyloid polypeptide (IAPP) fibrillation. IAPP fibrils have various deleterious effects, such as oxidative stress and disruption of cellular membrane integrity, resulting in pancreatic β-cell toxicity. Rutin, a plant polyphenol, possesses promising cytoprotective effects as a fibrillation inhibitor. Similarly, bioactive peptides have been identified as potential inhibitors to IAPP fibrillation. In this study, the effect of peptide/polyphenol mixtures consisting of rutin and each peptide, TNGQ, MANT, and YMSV, on anti-fibrillation activity and cellular response was elucidated. Results indicated a 54.7-75.1 % decrease in thioflavin T fluorescence, confirming anti-fibrillation activity. The combination decreased the average particle diameters of IAPP more than the single inhibitors, suggesting a combined effect of peptide/rutin mixtures in enhancing anti-fibrillation activity. IAPP fibrillation-induced rat insulinoma RIN-m cell death was minimized in the presence of the peptide/rutin mixture, but the activity was lower relative to rutin alone, suggesting a non-additive effect of the mixtures. Transmission electron microscopy showed a near-complete inhibition of IAPP fibrillation by TNGQ/rutin mixtures, which translated to a decreased production of membrane-bound IAPP oligomers in RIN-m cells based on immunofluorescence staining. Additionally, TNGQ/rutin mixtures significantly decreased reactive oxygen species production by 30 %, higher than the effects of single inhibitors, but no effect was observed on glucose-stimulated insulin secretion. The results demonstrate the potential of multifunctional compounds as dual inhibitor systems in controlling IAPP fibrillation and provide insight into the implications of peptide/polyphenol mixtures towards the rational development of novel anti-diabetic nutraceutical combinations.

The incidence rate of pancreatic cancer, a fatal illness with a meager 5-year survival rate, has been on the rise in recent times. When individuals accumulate excessive amounts of adipose tissue, the adipose organ becomes dysfunctional due to alterations in the adipose tissue microenvironment associated with inflammation and metabolism. This phenomenon may potentially contribute to the aberrant accumulation of fat that initiates pancreatic carcinogenesis, thereby influencing the disease's progression, resistance to treatment, and metastasis. This review presents a summary of the impact of pancreatic steatosis, visceral fat, cancer-associated adipocytes and lipid diets on the advancement of pancreatic cancer, as well as the reciprocal effects of pancreatic cancer on adipose tissue. Understanding the molecular mechanisms underlying the relationship between dysfunctional adipose tissue and pancreatic cancer better may lead to the discovery of new therapeutic targets for the disease's prevention and individualized treatment. This is especially important given the rising global incidence of obesity, which will improve the pancreatic cancer treatment options that are currently insufficient.

The Phenotypic states of vascular smooth muscle cells (SMCs) are essential to understanding vascular pathophysiology. SMCs in vessels generally express a specific set of contractile proteins, but decreased contractile protein expression, indicating a phenotypic shift, is a hallmark of vascular diseases. Recent studies have suggested the relation of abnormally high wall shear stress (WSS) of approximately 20 Pa with the aortic disease pathogenesis. However, due to the lack of appropriate experimental models to assess SMC phenotypic states, the details of the phenotypic shift under high WSS conditions remain unclear. In this study, we developed a coculture model where vascular endothelial cells (ECs) were cocultured with SMCs expressing calponin 1, a contractile protein involved in the phenotypic shift of SMCs. We investigated the effects of a pathologically high WSS condition on the phenotypic states of SMCs. Increased calponin 1 expression was found upon exposure to 20 Pa WSS compared with a physiological 2 Pa condition, whereas the expression of another contractile protein, α-smooth muscle actin (αSMA) remained unchanged. Furthermore, the inhibition of EC-derived nitric oxide (NO), which is associated with endothelial dysfunction in vascular diseases, resulted in a trend of decreasing αSMA and Calponin 1 expression under 20 Pa WSS conditions compared with 2 Pa. Our findings suggest that EC-derived NO under pathologically high WSS conditions may impact the expression of contractile proteins implicated in aortic pathophysiology.

New phosphate-modified nucleic acid derivatives are of great significance in basic research and biomedical applications. We have recently developed a new class of phosphoramide benzoazole oligonucleotides (PABAOs). In this work, th properties of N-benzoxazole oligodeoxyribonucleotides have been thoroughly examined. We have demonstrated the convenient automated solid-phase synthesis of oligomers with a different number of modifications (up to six) at various positions. Optical properties, thermal stability, structure, and dynamics of PABAO/DNA complexes have been investigated. The N-benzoxazole-modified phosphate group is uncharged at neutral pH and has a pKa value of 8.52. Structural analysis performed by the CD spectroscopy and MD simulation indicate B-form of PABAO/DNA duplexes. The thermal stability of PABAO/DNA complexes bearing N-benzoxazole is reduced by 2.5-6.2° per modification compared to native duplexes at standard and near physiological buffer conditions. The performed study underlines a great potential of phosphoramide benzoazole oligonucleotides for basic research, applied sciences, and biotechnology.

A successful embryo implantation relies heavily on the receptivity of the endometrial epithelium, a process regulated by various molecular mechanisms. Evaluating endometrial receptivity in infertility patients undergoing assisted reproductive treatment, particularly those with adenomyosis related infertility, poses significant challenges due to limitations associated with conventional assessment methods. In this study, we collected residual endometrial epithelial cells from the tips of embryo transfer catheters in patients with adenomyosis related infertility. High throughput sequencing revealed a marked downregulation of protein arginine methyltransferase 5 (PRMT5) in these cells. Functional assays demonstrated that PRMT5 interacts with and methylates homeobox A10 (HOXA10), a crucial transcription factor for endometrial receptivity and implantation. The methylation of HOXA10 at arginine 337 by PRMT5 enhances its stability and promotes the transcriptional activation of genes essential for endometrial differentiation and adhesion. The downregulation of PRMT5 led to decreased HOXA10 activity, resulting in impaired endometrial receptivity and subsequent implantation failure. These findings elucidate a critical pathway where PRMT5 downregulation negatively impacts HOXA10 function, providing new insights into the molecular mechanisms underlying implantation failure in adenomyosis related infertility. This study not only advances our understanding of the regulatory mechanisms governing endometrial receptivity but also identifies potential therapeutic targets for enhancing endometrial function in affected patients.

Metabolic diseases may be prevented by reducing carbohydrate intake and replacing plant-based diets with animal-based ones low in carbohydrates but high in protein, fat, and iron. While the effects of sugars on metabolic diseases are well-known, the role of iron remains unclear. This study aimed to explore the effects of a high-fat high-iron animal diet on body metabolism in mice. Micro-PET imaging was used to assess 18-F-labelled glucose uptake in BAT, and the morphology, respiratory function, and oxidative stress of BAT mitochondria were examined. The underlying mechanisms were elucidated by analyzing the expression of UCP-1, PGC-1α and PPARα. The high-iron high-fat diet increased appetite, impaired glucose tolerance, and reduced insulin sensitivity. Additionally, the high-iron diet promoted gluconeogenesis only in the absence of high-fat levels. Both high-iron and high-fat diets suppressed BAT activity, increased mitochondrial oxidative stress, decreased mitochondrial respiratory function, and lowered thermogenic gene expression. Weight loss strategies focusing solely on reducing carbohydrates and increasing animal foods, like ketogenic diets, may have long-term detrimental effects on metabolic health. Prioritizing dietary diversity and monitoring overall caloric intake is advisable for optimal outcomes.

Shiga toxin types 1 (Stx1) and 2 (Stx2), produced by Shiga toxin-producing Escherichia coli (STEC) and Shigella dysenteriae, are key virulence factors responsible for severe foodborne diseases, such as hemorrhagic colitis and hemolytic uremic syndrome (HUS). The receptors for Stxs are Gb3 and P1 glycotope, which contain the Galα1→4Gal epitope and are synthesized by human α1,4-galactosyltransferase (A4galt). Stx-related infections pose a global public health challenge, owing to the limited therapeutic options due to the restricted use of antibiotics. Therefore, there is an urgent need to develop novel therapeutic strategies. This study proposes an innovative strategy utilizing exosomes derived from CHO-Lec2 cells, which were modified with Functional-Spacer-Lipid (FSL) conjugates bearing the Gb3 carbohydrate epitope (exo-Gb3-FSL). Flow cytometry analysis confirmed the presence of Galα1→4Gal disaccharides on exo-Gb3-FSL constructs, enabling them to bind Stx1. Moreover, using CHO-Lec2 cells evaluated the ability of exo-Gb3-FSL agents to bind Stx1 and protect these cells from Stx1-mediated cytotoxicity. For Stx1-treated CHO-Lec2 cells, increased cell survival was observed when using 25 μM exo-Gb3-FSL constructs, compared to control cells. These findings highlight the potential of exosome-based anti-Stx1 agents as promising alternatives to conventional therapies. This innovative strategy may provide novel directions for studies on Stx1 neutralization, offering a valuable strategy for the treatment of Stx-related diseases.

Hypoxia inducible factor 2α (HIF-2α) is a member of the basic helix-loop-helix(bHLH)-Per-Arnt-Sim (PAS) family of transcription factors. It is overexpressed in several cancers, associated with poor prognosis of the patients and resistance to treatment. Here, we study the residues 366-704 of the C-terminal end of human HIF-2α, which contains the N-transcriptional activation domain (NTAD), the oxygen-dependent degradation domain (ODD), and a part of the inhibitory domain (IH). An efficient protocol was developed to produce the 366-704 domain of human HIF-2α protein. Subsequently, we analyzed its biophysical characteristics using circular dichroism spectroscopy and size exclusion chromatography showing that the protein forms an antiparallel beta sheet conformation, and a computational model of the HIF-2α structure was produced. Our data offer new structural information for the unique biological properties of HIF-2α.

Entinostat, a class I HDACs-selective inhibitor, is currently in clinical trials for treating cancers. In some of the trials, Entinostat treatment frequently causes hypophosphatemia and/or hypocalcemia. Moreover, the effect of Entinostat treatment on bone remains incompletely understood. In this study, we found that Entinostat treatment mildly increased the trabecular but not cortical bone volume, without compromising the bone strength, the numbers of Runx2-positive cells and TRAP-positive cells, and the serum levels of P1NP and TRAP-5b. Entinostat treatment significantly reduced the level of Runx2 mRNA but not Runx2 protein, and as a trend attenuated Ctsk expression. Furthermore, Entinostat treatment did not enhance MC3T3-E1 cell proliferation in vitro. These findings suggest that Entinostat increases trabecular bone volume not by regulating osteoblastogenesis or osteoclastogenesis, but possibly by attenuating the resorption capacity. Unexpectedly, Entinostat treatment increased the expression of Fgf23, whose protein is a hormone that regulates the serum level of phosphate (Pi). Meanwhile, Entinostat treatment increased the serum level of the active form (intact) Fgf23 and reduced that of Pi and calcium (Ca) as well. This study raised a concern about the anabolic effects of Entinostat in bone, and demonstrated that Entinostat treatment causes hypophosphatemia and hypocalcemia by upregulating Fgf23 mRNA and increasing intact Fgf23 protein in serum.

Methanogens, which are found exclusively in the Archaea domain of life, have the potential to help solve future energy challenges by producing methane. As a result, their metabolism has attracted significant attention in recent years. Despite being unable to grow on sugars, they store glycogen, which raises intriguing questions about the role of this polymer in methanogen metabolism and the signals that trigger its degradation when methanogenic substrates are not available. Here, we examined genomic databases to identify the enzymes responsible for glycogen synthesis and degradation in methanogens and explored the critical role of glycogen when nutrients and methanogenic substrates are scarce. Additionally, we analyzed the metabolic pathways involved in glycogen metabolism and their connection to the various types of methanogenesis exhibited by these organisms. Potential regulatory steps are proposed based on the reported effectors. Also, by employing the Alphafold3 server, the structural location of these sites in the enzyme structure was predicted, highlighting the advantages and limitations of this tool. Analysis of the allosteric effectors involved in this regulation suggests that energy charge may be the signal that triggers the metabolic switch from gluconeogenesis and glycogen storage to glycolysis and methanogenesis.

Although numerous approaches have emerged to address the challenges of critical limb ischemia (CLI), their clinical trials have proven elusive. Stem cell therapy has been utilized for CLI; however, its efficacy is limited, resulting in low survival rates in patients. Here, we investigated the impact of polydeoxyribonucleotide (PDRN) on the bioactivities of stem cells derived from human exfoliated deciduous teeth (SHED) against oxidative stress. PDRN treatment increased the proliferation, migration, antioxidant properties, and mitochondrial respiration of SHED. These beneficial effects were regulated by Akt activation. Through a murine hindlimb ischemia model, PDRN treatment demonstrated augmented the survival and proliferation of transplanted SHED at ischemic injury sites, whereas the inhibition of Akt suppressed these effects. Our findings revealed that PDRN promoted the therapeutic potential of SHED via Akt phosphorylation, suggesting PDRN-primed SHED as promising candidates for the development of novel stem cell therapeutics.

Regulated intramembrane proteolysis (RIP) is a fundamentally conserved mechanism involving sequential cleavage by a membrane-bound Site-1 protease (S1P) and a transmembrane Site-2 protease (S2P). In the opportunistic pathogen Pseudomonas aeruginosa, the alternate sigma factor σ activates alginate production and in turn is regulated by the MucABCD system. The anti-sigma factor MucA, which inhibits σ, is sequentially cleaved via RIP by AlgW (S1P) and MucP (S2P) respectively. In this study, we report high-resolution crystal structures of the MucP PDZ1 and PDZ2 domains. Structural and binding analysis confirms that MucP PDZ2 recognizes the carboxy-terminal Ala136 residue of MucA following Site-1 cleavage by AlgW, while the peptide binding groove of PDZ1 is obstructed by a short α-helix. A structure of MucP PDZ2 with bound MucA peptide shows how PDZ2 binds the newly exposed carboxyl terminus of MucA following AlgW cleavage. The ability of a ΔmucP strain of P. aeruginosa to form biofilms was reduced to a similar extent as a ΔalgW strain. This work paves the way for further studies of MucP and other PDZ-containing S2Ps in regulated intramembrane proteolysis.