The present invention provides compositions and methods for prevention, amelioration and treatment of gram positive bacteria, particularly Staphylococcal bacteria, with combinations of lysin, particularly Streptococcal lysin, particularly the lysin PlySs2, and one or more antibiotic, including daptomycin, vancomycin, oxacillin, linezolid, or related antibiotic(s).

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.

A di-enzymatic chimeric endolysin includes a primary enzymatic active domain including a primary protein sequence and that cleaves a glycosidic, peptide, or amide bond; a secondary enzymatic active domain disposed at a C-terminus end of the di-enzymatic chimeric endolysin and including a secondary protein sequence that, in combination with the primary enzymatic active domain, synergistically cleaves glycosidic, peptide, or amide bonds in a peptidoglycan; a cell wall binding domain including a recognition sequence that is sequentially interposed between the primary protein sequence and the secondary protein sequence and that binds to a cell wall; and a tertiary structure such that the primary enzymatic active domain faces and opposes the secondary enzymatic active domain in the di-enzymatic chimeric endolysin for synergistic cleavage of the peptidoglycan.

The present invention provides compositions and methods for prevention, amelioration and treatment of gram positive bacteria, particularly Staphylococcal bacteria, with combinations of lysin, particularly Streptococcal lysin, particularly the lysin PlySs2, and one or more antibiotic, including daptomycin, vancomycin, oxacillin, linezolid, or related antibiotic(s).

Polypeptides, viruses, methods and compositions provided herein are useful for the selective elimination of senescent cells. Method aspects include methods for inducing apoptosis in a senescent cell comprising administering to the cell a polynucleotide, virus, host cell, or pharmaceutical composition described herein. Other methods include expressing a pro-apoptotic gene in a senescent cell comprising administering to the cell the polynucleotide, virus, or pharmaceutical composition as described herein.

The present invention provides compositions and methods for prevention, amelioration and treatment of gram positive bacteria, particularly Staphylococcal bacteria, with combinations of lysin, particularly Streptococcal lysin, particularly the lysin PlySs2, and one or more antibiotic, including daptomycin, vancomycin, oxacillin, linezolid, or related antibiotic(s).

Disclosed herein include methods, compositions, and kits suitable for use in thresholding of protein signals. There are provided, in some embodiments, synthetic protein circuits that respond to inputs only above or below a certain threshold concentration. In some embodiments, the threshold value itself is tunable. Methods of treating a disease or disorder characterized by aberrant signaling are provided in some embodiments.

The present invention is generally related to engineered bacteriophages expressing antimicrobial peptides or lytic enzymes or fragments thereof for targeting a broad spectrum of bacterial hosts, and for the long-term suppression of bacterial phage resistance for reducing bacterial infections. In some embodiments, bacteriophages express antimicrobial peptides or antimicrobial polypeptides (e.g. phage lytic enzymes) which are secreted from the host bacteria, or alternatively released upon lysis of the bacterial host cell. Aspects of the present invention also relate to the use of the engineered bacteriophages for the reduction of bacterial infections, both in a subject or for bioremediation purposes, in clinical settings and wound healing.

The disclosure provides for methods, compositions, systems, devices, and kits for whole transcriptome amplification using stochastic barcodes.

The present invention relates to novel methods of generating and screening for chimeric polypeptides, which can be used in the treatment and prophylaxis of pathogenic bacterial contamination, colonisation and infection. The novel methods are based on random recombination of protein domains, and the chimeric polypeptides obtainable by the methods according to the invention are characterized in that they comprise at least one enzymatic active domain (EAD) and at least one cell binding domain (CBD). The present invention also relates to a library of chimeric polypeptides obtainable by the methods of the present invention.