Staphylococcus lactamase

Susceptible Gram-positive organisms such as Streptococcus pneumoniae and /3-lactamase-negative Staphylococcus aureus. 

Methicillin-resistent staphylococci are strains of staphylococci, which show resistance to a wide variety of antibiotics. They are named for their resistance to methicillin, a (3 -lactamase-resistant penicillin. Methicil-lin-resistante Staphylococcus aureus (MRSA) has become a serious problem particularly in hospitals. 

Staphylococcus aureus is responsible for a variety of skin infections which require therapeutic approaches different from those of streptococcal infections. Staphylococcal celluhtis is indistinguishable clinically from streptococcal cellulitis and responds to cloxacillin or flucloxacillin, but generally fails to respond to penicillin owing to penicillinase (/3-lactamase) production. Staphylococcus aureus is an important cause of superficial, localized skin sepsis which varies ftom small pustules to boils and occasionally to a more deeply invasive, suppurative skin abscess known as a carbuncle. Antibiotics are generally not indicated for these conditions. Pustules and boils settle with antiseptic soaps or creams and often discharge spontaneously, whereas carbuncles frequently require surgical drainage. Staphylococcus aureus may also cause... 

YAM T s, HAMILTON-MILLER J M T and SHAH s (1998) The effect of a component of tea Camellia sinensis) on methicillin resistance, PBP2 synthesis, and (J-lactamase production in Staphylococcus aureus, J Antimicrobial Chemtherapy, 42, 211-16. 

Human Viridans streptococci, Staphylococcus aureus, Eikenella corrodens, Elemophilus influenzae, and P-lactamase-producing anaerobic bacteria. 

The bacterium Staphylococcus aureus, which is a major cause of infection in the developed countries, is now resistant to most antibiotics. It is usually present on the skin, where it causes no problems, but it can invade the body through cuts and wounds, including those caused by surgery. These bacteria are now prevalent in many hospitals, so that infection is a major problem for the medical staff in hospitals. The resistant bacterium is known as methicillin-resistant Staphylococcus aureus (MRSA). It is also known in the mass media as the super bug . Penicillin kiUs bacteria because the P-lactam group in the antibiotic inhibits a reaction that is essential for bacterial ceU wall production. Consequently, the bacteria cannot proliferate. Resistance to penicillin in many bacteria is due to production of an enzyme, p-lactamase, that degrades P-lactams. The antibiotic methicillin is one of a group of semisynthetic penicillins in which the P-lactam group is not... 

An additional disadvantage with many penicillin and cephalosporin antibiotics is that bacteria have developed resistance to the drugs by producing enzymes capable of hydrolysing the P-lactam ring these enzymes are called P-lactamases. This type of resistance still poses serious problems. Indeed, methicillin is no longer used, and antibiotic-resistant strains of the most common infective bacterium Staphylococcus aureus are commonly referred to as MRSA (methicillin-resistant Staphylococcus aureus). The action of P-lactamase enzymes resembles simple base hydrolysis of an amide. 

Some organisms, such as Staphylococcus aureus, Neisseria gonorrhoeae, and Haemophilus influenzae, may produce -lactamase and therefore be resistant to penicillin and its congeners. Testing for 3-lactamase production by isolates enables an early decision on the use of penicillin and congeners in treatment of the disease. 

Nafcillin, oxacillin, cloxacillin, and dicloxacillin are more resistant to bacterial (3-lactamases than is penicillin G. Consequently, these antibiotics are effective against streptococci and most community-acquired penicillinase-producing staphylococci. Methicillin, which is no longer marketed in the United States, is another penicillinase-resistant antibiotic similar to nafcillin and oxacillin. For historical reasons, staphylococci resistant to oxacillin or nafcillin are labeled methicillin resistant. Many hospitals are reservoirs for MRSA and methi-cillin-resistant Staphylococcus epidermidis (MRSE). These nosocomial pathogens are resistant in vitro to all (3-lactam antibiotics. 

Staphylococcus aureus - [ANTIBIOTICS - BETA-LACTAMS - CEPHALOSPORINS] (Vol 3) - [DISINFECTANTS AND ANTISEPTICS] (Vol 8) - [ANTIBIOTICS - BETA-LACTAMS - BETA-LACTAMASE INHIBITORS] (Vol 3) - [ANTIBIOTICS - LINCOSAMINIDES] (Vol3) - [ANTIBIOTICS - BETA-LACTAMS - PENICILLINS AND OTHERS] (Vol 3) - [ANTIBIOTICS-AMINOGLYCOSIDES] (Vol2) - [ANTIBIOTICS - GLYCOPEPTIDES(DALBAHEPTIDES)] (Vol 2) -bacitracin resistance [ANTIBIOTICS - PEPTIDES] (Vol 3) -ethanol activity against [DISINFECTANTS AND ANTISEPTICS] (Vol 8) -inhibited by sorbates [SORBIC ACID] (Vol 22)... 

Figure B3.5.12 Effect of mutations detected by CD. The far-UV CD spectra (A) show that the secondary structure of p-lactamase PC1 (solid line) from Staphylococcus aureus is essentially unaffected by point mutations P2 (Thr 140—>lle dashed line) and P54 (Asp 146->Asn dotted line). The crystallographic structure of P54 (Herzberget al., 1991) confirms that, apart from a loop region, the main body of the molecule that contains the thirteen tyrosine residues is very closely similar to that in the wild-type enzyme. The intensity of the tyrosine ellipticity (B) is, however, markedly decreased in each of the mutants, the lower thermodynamic stabilities of which support the interpretation of increased dynamics (Craig et al., 1985).

Craig, S., Hollecker, M., Creighton, T.E., and Pain, R.H. 1985. Single amino acid mutations block a late step in the folding of fl-lactamase from Staphylococcus aureus. J. Mol. Biol. 185 681-687. 

Herzberg, O., Kapadia, G., Blanco, B., Smith, T.S., and Coulson, A. 1991. Structural basis for the inactivation of the P54 mutant of P-lactamase from Staphylococcus aureus PCI. Biochemistry 30 9503-9509. 

Fig. 2. Amino acid sequences of /3-lactamases of Staphylococcus aureus PCI (upper line) and of BadUus lickeniformis 749/C ments LA to LE, lower line). Matching residues are shown in block letters (upper line). (From Ambler and Meadway, 63.)... 

Cephalosporins have been classified as first, second or third generation, largely on the basis of bacterial susceptibility patterns and resistance to p-lactamases (Figure 30.8). [Note They are ineffective against methicillin-resistant Staphylococcus aureus (MRSA), Listeria monocytogenes. Clostridium diffidle and the enterococci.]... 

A major mechanism of acquired resistance to the penicillins is bacterial production of enzymes called P-lactamases. These enzymes hydrolyze the penicillin P lactam ring that is necessary for its activity. p-Lactamases with a strong proclivity for penicillins are called penicillinases. Because most strains of Staphylococcus aureus and many strains of Staphylococcus epidermidis produce penicillinase, penicillins G andV are not effective against these gram-positive bacteria. 

Destroying the Trojan horse. Penicillin is hydrolyzed and thereby rendered inactive by penicillinase (also known as P-lactamase), an enzyme present in some resistant bacteria. The mass of this enzyme in Staphylococcus aureus is 29.6 kd. The amount of penicillin hydrolyzed in 1 minute in a 10-ml solution containing 10 9 g of purified penicillinase was measured as a function of the concentration of penicillin. Assume that the concentration of penicillin does not change appreciably during the assay. 

Although much of the early work on the j3-lactamases was carried out with Gram-positive bacteria such as B. cereus [171], B. licheniformis [172] and Staphylococcus aureus [173], recent studies have shown the enzymes to play an important role in resistance of the enterobacteraceae and Ps. aeruginosa to the /3-lactam antibiotics [141]. 

---