The scavenging capacity of DMBT1 is impaired by germline deletions.

The Scavenger Receptor Cysteine-Rich (SRCR) proteins are an archaic group of proteins characterized by the presence of multiple SRCR domains. They are membrane-bound or secreted proteins, which are generally related to host defense systems in animals. Deleted in Malignant Brain Tumors 1 (DMBT1) is a SRCR protein which is secreted in mucosal fluids and involved in host defense by pathogen binding by its SRCR domains. Genetic polymorphism within DMBT1 leads to DMBT1-alleles giving rise to polypeptides with interindividually different numbers of SRCR domains, ranging from 8 SRCR domains (encoded by 6 kb DMBT1 variant) to 13 SRCR domains (encoded by the 8 kb DMBT1 variant). In the present study, we have investigated whether reduction from 13 to 8 amino-terminal SRCR domains leads to reduction of bacterial binding. The 6 kb variant bound ~20-45% less bacteria compared to the 8 kb variant. These results support the hypothesis that genetic variation in DMBT1 may influence microbial defense.

Comparable efficacies of the antimicrobial peptide human lactoferrin 1-11 and gentamicin in a chronic methicillin-resistant Staphylococcus aureus osteomyelitis model.

The therapeutic efficacy of an antimicrobial peptide, human lactoferrin 1-11 (hLF1-11), was investigated in a model of chronic methicillin-resistant Staphylococcus aureus (MRSA) (gentamicin susceptible) osteomyelitis in rabbits. We incorporated 50 mg hLF1-11/g or 50 mg gentamicin/g cement powder into a calcium phosphate bone cement (Ca-P) and injected it into the debrided tibial cavity, creating a local drug delivery system. The efficacy of hLF1-11 and gentamicin was compared to that of a sham-treated control (plain bone cement) (n=6) and no treatment (infected only) (n=5). The results were evaluated by microbiology, radiology, and histology. MRSA was recovered from all tibias in both control groups (n=11). On the other hand, hLF1-11 and gentamicin significantly reduced the bacterial load. Furthermore, no growth of bacteria was detected in five out of eight and six out of eight specimens of the hLF1-11- and gentamicin-treated groups, respectively. These results were confirmed by a significant reduction of the histological disease severity score by hLF1-11 and gentamicin compared to both control groups. The hLF1-11-treated group also had a significantly lower radiological score compared to the gentamicin-treated group. This study demonstrates the efficacy of hLF1-11 incorporated into Ca-P bone cement as a possible therapeutic strategy for the treatment of osteomyelitis, showing efficacy comparable to that of gentamicin. Therefore, the results of this study warrant further preclinical investigations into the possibilities of using hLF1-11 for the treatment of osteomyelitis.

In vivo comparison of Dhvar-5 and gentamicin in an MRSA osteomyelitis prevention model.

OBJECTIVES: The continued rise in drug-resistant pathogens has led to global research efforts into new antimicrobial agents. A promising class of new agents are the antimicrobial peptides. The aim of the study was to investigate the efficacy of the antimicrobial peptide Dhvar-5 in a prophylactic, methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis model. METHODS: Dhvar-5 (12 mg or 24 mg/rabbit) was incorporated into polymethyl methacrylate (PMMA) beads as a local drug delivery system. For comparison, plain beads (control) and beads containing gentamicin as a sulphate (10 mg or 24 mg per rabbit) were also prepared. The beads were inserted into the inoculated femoral cavity of 36 rabbits, and 1 week later they were killed. The presence and severity of MRSA osteomyelitis was assessed by culture and histology. RESULTS: Both the 24 mg Dhvar-5 beads and the 24 mg gentamicin sulphate beads significantly reduced the bacterial load of the inoculated femora compared with the control chain. Although a 24 mg Dhvar-5 dose inhibited MRSA growth, it did not completely sterilize the femora. Sterilization occurred only in some of the gentamicin-treated specimens. CONCLUSION: We conclude that both the gentamicin beads and the Dhvar-5 beads were only partially effective at preventing MRSA infection in this model.

Inadequate salivary flow and poor oral mucosal status in intubated intensive care unit patients.

OBJECTIVE: To investigate salivary flow and frequency of oral mucositis in intensive care unit patients compared with patients admitted because of elective coronary artery bypass graft (CABG) surgery. In addition, the pattern of oropharyngeal colonization was investigated in these patients. DESIGN: Prospective study. SETTING: Mixed intensive care unit and cardiosurgical ward. PATIENTS: In this study, 24 ventilated intensive care unit patients and 20 CABG patients were included. MEASUREMENTS AND MAIN RESULTS: Two dental hygienists examined intensive care unit patients for the presence of periodontal disease and mucositis at admission and subsequently every week during their stay in the intensive care unit. At the same time, stimulated salivary flow and salivary total immunoglobulin A output were measured. Oropharyngeal cultures were obtained as well. CABG patients were examined the day before the operation, 1 day, 1 wk, and 2 wks after the operation. The following results were obtained: a) temporarily reduced postoperative stimulated salivary flow and total salivary immunoglobulin A output in CABG patients and nearly absent stimulated salivary flow in intensive care unit patients; b) oropharyngeal colonization with potentially pathogenic microorganisms in intensive care unit and not in CABG patients; and c) the increase in mucositis index in intensive care unit patients paralleled the increase in potentially pathogenic microorganism oropharyngeal colonization, especially and. CONCLUSIONS: Absence of adequate salivary flow in intubated intensive care unit patients causes severe xerostomia, which may contribute to the development of mucositis and oropharyngeal colonization with Gram-negative bacteria.

High levels of sulfated mucins in bronchoalveolar lavage fluid of ICU patients with ventilator-associated pneumonia.

OBJECTIVE: To compare the levels of sulfated mucins in bronchoalveolar lavage fluid (BALF) in ICU patients with ventilator-associated pneumonia (VAP) with those in non-infectious controls, i.e., ventilated ICU patients without VAP, and nonventilated patients. DESIGN AND SETTING: Prospective study in a mixed intensive care unit and outpatient clinic of a university hospital. PATIENTS: The study included 56 ventilated ICU patients with VAP, 21 ventilated ICU patients without VAP, and 26 nonventilated outpatients with no pulmonary infection. MEASUREMENTS AND RESULTS: Total cell count and differential cell count of BALF samples were determined, and sulfated mucin levels were measured. For this we used the monoclonal antibody F2 against the sulfated Lewis C structure (SO(3)-3Galbeta1-3GlcNAc). Sulfated mucin levels were significantly increased in ICU patients with VAP than in those without VAP and nonventilated patients. No statistical difference was found between the two groups of ICU patients regarding APACHE II score and the duration of mechanical ventilation prior to the bronchoalveolar lavage. CONCLUSIONS: The increased levels of sulfated mucins in ICU patients with VAP are associated with infection and not with ventilation. The increase in sulfated mucins may favor the persistence of those micro-organisms that possess mucin sulfatase activity, which enable them to survive within the mucus, especially Pseudomonas aeruginosa.

The influence of antimicrobial peptides and mucolytics on the integrity of biofilms consisting of bacteria and yeasts as affecting voice prosthetic air flow resistances.

The integrity of biofilms on voice prostheses used to rehabilitate speech in laryngectomized patients causes unwanted increases in airflow resistance, impeding speech. Biofilm integrity is ensured by extracellular polymeric substances (EPS). This study aimed to determine whether synthetic salivary peptides or mucolytics, including N-acetylcysteine and ascorbic acid, influence the integrity of voice prosthetic biofilms. Biofilms were grown on voice prostheses in an artificial throat model and exposed to synthetic salivary peptides, mucolytics and two different antiseptics (chlorhexidine and Triclosan). Synthetic salivary peptides did not reduce the air flow resistance of voice prostheses afterm biofilm formation. Although both chlorhexidine and Triclosan reduced microbial numbers on the prostheses, only the Triclosan-containing positive control reduced the air flow resistance. Unlike ascorbic acid, the mucolytic N-acetylcysteine removed most EPS from the biofilms and induced a decrease in air flow resistance.