Abstract: The present disclosure is directed to lysin-AMP polypeptide constructs, isolated lysin polypeptides, and pharmaceutical compositions comprising the isolated polypeptides and/or lysin-AMP polypeptide constructs. Methods of using the lysin-AMP polypeptide constructs, isolated lysin polypeptides and pharmaceutical compositions are also herein provided. In addition, isolated polynucleotides encoding the lysin-AMP polypeptide constructs and isolated lysin polypeptides are disclosed herein.

Abstract: The present disclosure is directed to lysin-AMP polypeptide constructs, isolated lysin polypeptides, and pharmaceutical compositions comprising the isolated polypeptides and/or lysin-AMP polypeptide constructs. Methods of using the lysin-AMP polypeptide constructs, isolated lysin polypeptides and pharmaceutical compositions are also herein provided. In addition, isolated polynucleotides encoding the lysin-AMP polypeptide constructs and isolated lysin polypeptides are disclosed herein.

Abstract: The present invention provides methods for the prevention, control, disruption and treatment of bacterial biofilms with lysin, particularly lysin having capability to kill Staphylococcal bacteria, including drug resistant Staphylococcus aureus, particularly the lysin PlySs2. The invention also provides compositions and methods for use in treatment or modulation of bacterial biofilm(s) and biofilm formation.

Abstract: Disclosed herein are preventing or treating a bacterial infection caused by at least one species of Gram-positive bacteria, the method comprising co-administering to a subject diagnosed with, at risk for, or exhibiting symptoms of a bacterial infection a first amount of a modified lysin polypeptide and a second amount of an antibiotic suitable for the treatment of a Gram-positive bacterial infection. Further disclosed herein are methods of augmenting the efficacy of an antibiotic or reducing the development of antibiotic resistance.

Abstract: The present disclosure provides methods and compositions useful for the prophylactic and therapeutic amelioration and treatment of infections caused by Gram-negative bacteria, including Pseudomonas aeruginosa. The disclosure further provides compositions and methods of incorporating and utilizing lysin polypeptides of the present disclosure for augmenting the efficacy of antibiotics generally suitable for the treatment of Gram-negative bacterial infection.

Abstract: The present disclosure is directed to lysin-AMP polypeptide constructs, isolated lysin polypeptides, and pharmaceutical compositions comprising the isolated polypeptides and/or lysin-AMP polypeptide constructs. Methods of using the lysin-AMP polypeptide constructs, isolated lysin polypeptides and pharmaceutical compositions are also herein provided, including methods of treating a bacterial infection of an organ or tissue in which pulmonary surfactant is present or Gram-negative bacterial infections that are associated with a biofilm. In addition, isolated polynucleotides encoding the lysin-AMP polypeptide constructs and isolated lysin polypeptides are disclosed herein.

Abstract: The present disclosure is directed to a lysin-AMP polypeptide construct comprising: (a) a first component comprising the polypeptide sequence of: (i) SEQ ID NO: 118 (GN202); or (ii) a polypeptide having lysin activity and having at least 80% sequence identity with the polypeptide sequence of SEQ ID NO: 118 (GN202); or (iii) an active fragment of SEQ ID NO: 118 (GN202); and (b) a second component comprising the polypeptide sequence of at least one antimicrobial peptide (AMP), wherein the at least one AMP comprises SEQ ID NO: 114 (FIRL). Exemplary lysin-AMP polypeptides, such as GN370 (SEQ ID NO: 44) as well as methods of treating bacterial infections using the present lysin-AMP polypeptide constructs are also disclosed.

Abstract: Disclosed herein are pharmaceutical compositions comprising an effective amount of an isolated Chp peptide having an amino acid sequence selected from the group consisting of SEQ ID NOs. 81-91 and 94-102, or a modified Chp peptide having about 80% sequence identity therewith, wherein the modified Chp peptide inhibits growth, reduces the population, or kills at least one species of Gram-negative or acid-fast bacteria; and a pharmaceutically acceptable carrier. Further disclosed herein are isolated Chp peptides, as well as vectors comprising a nucleic acid molecule that encode the Chp peptides and host cells comprising a vector. Also disclosed herein are methods of inhibiting the growth, reducing the population, or killing of at least one species of Gram-negative or acid-fast bacteria, methods of treating a bacterial infection in a subject, and methods for prevention, disruption, or treatment of a biofilm comprising a Gram-negative bacteria.

Abstract: The present invention provides methods for the prevention, control, disruption and treatment of bacterial biofilms with lysin, particularly lysin having capability to kill Staphlococcal bacteria, including drug resistant Staphylococcus aureus, particularly the lysin PlySs2. The invention also provides compositions and methods for use in treatment or modulation of bacterial biofilm(s) and biofilm formation.

Abstract: The present disclosure relates to methods for restoring or augmenting bactericidal activity of an antibiotic in an organ or tissue in which pulmonary surfactant is present. More specifically, the present disclosure describes that inhibition of antibiotics due to environmental factors, such as the presence of pulmonary surfactant in an organ or tissue such as the respiratory epithelium can be sidestepped or overcome and the effectiveness of the antibiotic in that milieu restored or augmented by co-administration of an antibiotic and a lysin.

Abstract: The present disclosure provides methods and compositions useful for the prophylactic and therapeutic amelioration and treatment of infections caused by Gram-negative bacteria, including Pseudomonas aeruginosa. The disclosure further provides compositions and methods of incorporating and utilizing lysin polypeptides of the present disclosure for augmenting the efficacy of antibiotics generally suitable for the treatment of Gram-negative bacterial infection.

Abstract: The present disclosure is directed to a method of treating or preventing a bone or joint infection, which method comprises: administering a therapeutically effective amount of a PlySs2 lysin comprising the amino acid sequence of SEQ ID NO: 1 or a variant thereof having at least 80% identity to SEQ ID NO: 1, wherein the variant comprises bacteriocidal and/or bacteriostatic activity against the Gram-positive bacteria, to a subject in need thereof, optionally co-administered with one or more antibiotics, wherein the bone or joint infection comprises a Gram-positive bacteria, such as Staphylococcus epidermidis or Staphylococcus aureus. Methods for preventing or disrupting a Gram-positive bacterial biofilm formed in a synovial fluid, such as a biofilm formed by Staphylococcus epidermidis, are also disclosed.

Abstract: The present disclosure relates to methods for restoring or augmenting bactericidal activity of an antibiotic in an organ or tissue in which pulmonary surfactant is present. More specifically, the present disclosure describes that inhibition of antibiotics due to environmental factors, such as the presence of pulmonary surfactant in an organ or tissue such as the respiratory epithelium can be sidestepped or overcome and the effectiveness of the antibiotic in that milieu restored or augmented by co-administration of an antibiotic and a lysin.

Abstract: Disclosed are novel lysin polypeptides active against Gram-negative bacteria, particularly P. aeruginosa, pharmaceutical compositions containing them and methods for their use to treat Gram-negative bacterial infections and more generally to inhibit the growth, or reduce the population, or kill Gram-negative bacteria, including without limitation disrupting biofilms formed by such bacteria. Certain of the disclosed lysins have been modified in amino acid sequence compared to that of lysins by replacement of certain charged amino acids with noncharged amino acids and/or by fusion at the N- or C-terminus with antibacterial peptide sequences with or without an intervening linker.

Abstract: The present disclosure is directed to a method of treating or preventing infective endocarditis due to Gram-positive bacteria, such as S. aureus, which method includes administering a therapeutically effective amount of a combination of one or more antibiotics, optionally at a sub-Minimum Inhibitory Concentration (MIC) level, and a PlySs2 lysin, such as a single dose of PlySs2 lysin at a sub-MIC level, wherein the one or more antibiotics and the PlySs2 lysin are administered simultaneously or sequentially to a subject in need thereof in any order.

Abstract: The present invention provides methods, assays, compositions, formulations, and constructs, particularly lytic peptide constructs, which relate to and are based on the activity and use of blood components, particularly serum albumin and lysozyme, and their activity and use to enhance or synergize with the bacterial killing effect of anti-bacterial lytic proteins and peptides.

Abstract: Provided are polypeptides and compositions comprising the polypeptides for use in killing and/or inhibiting growth of Gram-negative bacteria, particularly P. aeruginosa. The polypeptides are contiguous polypeptides (lysocins) that contain an engineered bacteriocin segment that can be translocated through an outer membrane channel of the Gram-negative bacteria, such as Domain I of the S-type poycin from P. aeruginosa bacterocin pyocin S2 (PyS2) linked to a lysin catalytic segment that has peptidoglycan (PG) hydrolase activity. The lysin catalytic segment can be a catalytic segment of GN4 lysin or any other lysin catalytic segment or a hydrolytic enzyme thereof that has PG hydrolase activity.

Abstract: The present disclosure is directed to lysin-AMP polypeptide constructs, isolated lysin polypeptides, and pharmaceutical compositions comprising the isolated polypeptides and/or lysin-AMP polypeptide constructs. Methods of using the lysin-AMP polypeptide constructs, isolated lysin polypeptides and pharmaceutical compositions are also herein provided, including methods of treating a bacterial infection of an organ or tissue in which pulmonary surfactant is present or Gram-negative bacterial infections that are associated with a biofilm. In addition, isolated polynucleotides encoding the lysin-AMP polypeptide constructs and isolated lysin polypeptides are disclosed herein.

Abstract: Acinetobacter lysin polypeptides and variants peptides with killing activity against gram negative bacteria. Methods for treating bacterial infections or bacterial colonization using Acintobacter lysin polypeptides.

Abstract: Disclosed herein are pharmaceutical compositions comprising an effective amount of an isolated Chp peptide having an amino acid sequence selected from the group consisting of SEQ ID NOs. 1-4, 6-26 and 54-66, or a modified Chp peptide having about 80% sequence identity therewith, wherein the modified Chp peptide inhibits growth, reduces the population, or kills at least one species of Gram-negative bacteria; and a pharmaceutically acceptable carrier. Further disclosed herein are isolated Chp peptides, as well as vectors comprising a nucleic acid molecule that encode the Chp peptides and host cells comprising a vector. Also disclosed herein are methods of inhibiting the growth, reducing the population, or killing of at least one species of Gram-negative bacteria and methods of treating a bacterial infection in a subject.