2' Life-changing minutes: impact evaluation of a novel health promotion format on cancer prevention.

Cancer is one of the most important societal challenges in the world, with over 23 million new cases/year and 10 million deaths/year, that will only be properly tackled with a stronger focus on prevention. This calls for an informed population, aware of risk factors and willing to adopt preventive behaviors and early cancer screenings. For that purpose, 2' Life-changing minutes was created, the first ever televised Entertainment-Education series on cancer prevention. This study aims to evaluate the impact of 2' Life-changing minutes, a novel E-E format for cancer prevention, on knowledge gains and behavior changes. Two complementary studies were performed involving a total of 1314 participants: a test-screening (TS) study targeting potential viewers of the series, and a natural-screening (NS) study targeting those that spontaneously watched the series on television. We found (i) very high levels of appreciation and narrative engagement, and also willingness to see more episodes; (ii) statistically significant knowledge gains, ranging from 17% to 44%, on all four topics tested; (iii) evidence of effective behavior change. Regression analysis showed that narrative engagement was the best predictor of behavior change [NS: odds ratio (OR) = 3.38, 95% confidence interval (CI) = 1.70-6.74, p = 0.001; TS: OR = 2.05, 95% CI = 1.13-0.371, p = 0.018]. This study demonstrates the series' real impact and serves as a proof-of-concept for a novel strategy of cancer prevention that is based around compelling health narratives, rather than information or data, to engage viewers, increase knowledge and induce behavior change.

An Evolved Strain of the Oleaginous Yeast Rhodotorula toruloides, Multi-Tolerant to the Major Inhibitors Present in Lignocellulosic Hydrolysates, Exhibits an Altered Cell Envelope.

The presence of toxic compounds in lignocellulosic hydrolysates (LCH) is among the main barriers affecting the efficiency of lignocellulose-based fermentation processes, in particular, to produce biofuels, hindering the production of intracellular lipids by oleaginous yeasts. These microbial oils are promising sustainable alternatives to vegetable oils for biodiesel production. In this study, we explored adaptive laboratory evolution (ALE), under methanol- and high glycerol concentration-induced selective pressures, to improve the robustness of a Rhodotorula toruloides strain, previously selected to produce lipids from sugar beet hydrolysates by completely using the major C (carbon) sources present. An evolved strain, multi-tolerant not only to methanol but to four major inhibitors present in LCH (acetic acid, formic acid, hydroxymethylfurfural, and furfural) was isolated and the mechanisms underlying such multi-tolerance were examined, at the cellular envelope level. Results indicate that the evolved multi-tolerant strain has a cell wall that is less susceptible to zymolyase and a decreased permeability, based on the propidium iodide fluorescent probe, in the absence or presence of those inhibitors. The improved performance of this multi-tolerant strain for lipid production from a synthetic lignocellulosic hydrolysate medium, supplemented with those inhibitors, was confirmed.

Phylogeography of the red alga Gracilariopsis tenuifrons (Gracilariales) along the Brazilian coast.

Changes in the sea level during the Holocene are regarded as one of the most prevalent drivers of the diversity and distribution of macroalgae in Brazil, influenced by the emergence of the Vitória-Trindade seamount chain (VTC). Gracilariopsis tenuifrons has a wide geographic distribution along the Brazilian coast, from Maranhão state (2°48'64.3" S) to Santa Catarina state (27.5°73'83" S). The knowledge of historical processes affecting diversity may allow the development of conservation strategies in environments against anthropogenic influence. Therefore, knowledge about phylogeography and populational genetic diversity in G. tenuifrons is necessary. Six populations were sampled along the northeastern tropical (Maranhão-MA, Rio Grande do Norte-RN, Alagoas-AL, and Bahia-BA States) and southeastern subtropical (São Paulo "Ubatuba"-SP1 and São Paulo "Itanhaém"-SP2 States) regions along the Brazilian coast. The genetic diversity and structure of G. tenuifrons were inferred using mitochondrial (COI-5P and cox2-3 concatenated) DNA markers. Gracilariopsis tenuifrons populations showed an evident separation between the northeast (from 2°48'64.3" S to 14°18'23" S; 17 haplotypes) and the southeast (from 23°50'14.9" S to 24°20'04.7" S; 10 haplotypes) regions by two mutational steps between them. The main biogeographical barrier to gene flow is located nearby the VTC. The southeast region (São Paulo State) is separated by two subphylogroups (SP1, three haplotypes and SP2, six haplotypes), and Santos Bay (estuary) has been considered a biogeographical barrier between them. The presence of genetic structure and putative barriers to gene flow are in concordance with previous studies reporting biogeographic breaks in the southwest Atlantic Ocean, including the genetic isolation between northeast and southeast regions for red and brown algae in the vicinity of the VTC.

Development and process evaluation of a new entertainment-education TV series for cancer prevention in Portugal.

Cancer is a primary societal challenge worldwide, with over 23 million new cases/year, and 10 million deaths/year. Estimates of preventable cancer deaths rise as high as 70%, but such estimates rely heavily on individual behaviors, which in turn are correlated with knowledge and attitudes towards health and cancer. This paper describes the iterative evidence-based development of the first entertainment-education series on cancer prevention to be televised, and reports its effectiveness evaluation. A nominal group defined the guiding principles that were translated into key characteristics for a series named '2' Life-changing minutes'. Pilot episodes were produced and evaluated in two complementary studies-a focus group study with medical doctors and a survey study with prospective viewers. Results from these studies guided the optimization and production of the full series, which was broadcast on national public TV, in prime time. An evaluation study was performed afterwards with naturally-occurring viewers and results show audience reach on par with purely entertainment series, that health messages can be clearly conveyed through fictional narratives, and that the series has high levels of appreciation and health promotion potential. '2' Life-changing minutes' constitutes a novel and effective proposal for health promotion, that challenges the primacy of information and statistics still common in health communication, with a new format based on stories, characters and social contexts to successfully promote health.

Brazilian marine phylogeography: A literature synthesis and analysis of barriers.

In the last 30 years a plethora of phylogeography studies have been published targeting Brazilian marine species. To date, several historical and extant physical and ecological processes have been identified as drivers of allopatric, sympatric and parapatric population genetic differentiation detected along the Brazilian coast. Examples of extant physical barriers include the split of the South Equatorial Current into the Brazil and North Brazil boundary currents, the mouth of major rivers (e.g., Amazon, São Francisco and Doce rivers) and coastal upwellings. Examples of historical barriers include the Vitória-Trindade seamount chain promoting genetic differentiation during periods of glacial maxima and lower sea levels. Examples of ecological speciation include adaptations to different substrata, resource use and reproductive biology. We used published data to build data sets and generalized additive models to identify patterns of spatial phylogeographical concordance across multiple taxa and markers. Our results identify Cape São Roque as the most dominant extant barrier to gene flow along the Brazilian coast, followed by the Vitória-Trindade seamount chain and Cape Santa Marta. Cape Santa Marta is the northern winter limit of the Rio da Plata plume and is intermittently influenced by the Malvinas Current. This study provides a novel explicit quantitative approach to comparative phylogeography that recognizes four Brazilian phylogeographical regions delimited by processes associated with barriers to gene flow.

Role of the Hydrophobic Bridge in the Carbapenemase Activity of Class D ß-Lactamases.

Class D carbapenemases are enzymes of the utmost clinical importance due to their ability to confer resistance to the last-resort carbapenem antibiotics. We investigated the role of the conserved hydrophobic bridge in the carbapenemase activity of OXA-23, the major carbapenemase of the important pathogen Acinetobacter baumannii We show that substitution of the bridge residue Phe110 affects resistance to meropenem and doripenem and has little effect on MICs of imipenem. The opposite effect was observed upon substitution of the other bridge residue Met221. Complete disruption of the bridge by the F110A/M221A substitution resulted in a significant loss of affinity for doripenem and meropenem and to a lesser extent for imipenem, which is reflected in the reduced MICs of these antibiotics. In the wild-type OXA-23, the pyrrolidine ring of the meropenem tail forms a hydrophobic interaction with Phe110 of the bridge. Similar interactions would ensue with ring-containing doripenem but not with imipenem, which lacks this ring. Our structural studies showed that this interaction with the meropenem tail is missing in the F110A/M221A mutant. These data explain why disruption of the interaction between the enzyme and the carbapenem substrate impacts the affinity and MICs of meropenem and doripenem to a larger degree than those of imipenem. Our structures also show that the bridge directs the acylated carbapenem into a specific tautomeric conformation. However, it is not this conformation but rather the stabilizing interaction between the tail of the antibiotic and the hydrophobic bridge that contributes to the carbapenemase activity of class D ß-lactamases.

Perioperative ultrasound applied to diagnosis and decision making in anesthesia.

INTRODUCTION: Ultrasound is a portable and safe technology that is increasingly used to assist anesthetic procedures and has been integrated into the routine practice of a wide range of invasive procedures. As a complementary diagnostic tool, publications related to perioperative support other than vascular access and nerve blocks are currently lacking. EVIDENCE ACQUISITION: Given the growing interest of anesthesiologists in acquisition of knowledge and skills of ultrasound, we propose a systematic review of the diagnosis, decision making or change in perioperative management of non-cardiac surgical patients derived from ultrasound practice. Of 1112 references found in electronic databases, 62 studies resulted from the screening process. EVIDENCE SYNTHESIS: A complete critical reading of 19 full-text publications was carried out with quantitative analysis of 1825 ultrasound examinations including echocardiography, neck and laryngeal ultrasound, pulmonary ultrasound and abdominal ultrasound, all of them performed by anesthesiologists. Diagnosis applied ultrasound and decision making during perioperative period resulted in change in the management of 31% with 95% CI of 21.06 to 42.04 and odds ratio of 2.68 (1.77 to 4.06) related to hemodynamic, airway and respiratory perioperative management. CONCLUSIONS: Since most of the articles included in this review are observational studies with inherent design concerns, there is an urgent requirement for randomized controlled trials in this area. As anesthesiologists become more comfortable and knowledgeable in ultrasound applied to the perioperative support, emergence of protocols with multidisciplinary ultrasound exploration is expected to allow an improvement in perioperative safety.

The role of conserved surface hydrophobic residues in the carbapenemase activity of the class D ß-lactamases.

Carbapenem-hydrolyzing class D ß-lactamases (CHDLs) produce resistance to the last-resort carbapenem antibiotics and render these drugs ineffective for the treatment of life-threatening infections. Here, it is shown that among the clinically important CHDLs, OXA-143 produces the highest levels of resistance to carbapenems and has the highest catalytic efficiency against these substrates. Structural data demonstrate that acylated carbapenems entirely fill the active site of CHDLs, leaving no space for water molecules, including the deacylating water. Since the entrance to the active site is obstructed by the acylated antibiotic, the deacylating water molecule must take a different route for entry. It is shown that in OXA-143 the movement of a conserved hydrophobic valine residue on the surface opens a channel to the active site of the enzyme, which would not only allow the exchange of water molecules between the active site and the milieu, but would also create extra space for a water molecule to position itself in the vicinity of the scissile bond of the acyl-enzyme intermediate to perform deacylation. Structural analysis of the OXA-23 carbapenemase shows that in this enzyme movement of the conserved leucine residue, juxtaposed to the valine on the molecular surface, creates a similar channel to the active site. These data strongly suggest that all CHDLs may employ a mechanism whereupon the movement of highly conserved valine or leucine residues would allow a water molecule to access the active site to promote deacylation. It is further demonstrated that the 6α-hydroxyethyl group of the bound carbapenem plays an important role in the stabilization of this channel. The recognition of a universal deacylation mechanism for CHDLs suggests a direction for the future development of inhibitors and novel antibiotics for these enzymes of utmost clinical importance.

Pathophysiology, Diagnosis and Treatment of Somatosensory Tinnitus: A Scoping Review.

Somatosensory tinnitus is a generally agreed subtype of tinnitus that is associated with activation of the somatosensory, somatomotor, and visual-motor systems. A key characteristic of somatosensory tinnitus is that is modulated by physical contact or movement. Although it seems common, its pathophysiology, assessment and treatment are not well defined. We present a scoping review on the pathophysiology, diagnosis, and treatment of somatosensory tinnitus, and identify priority directions for further research. Methods: Literature searches were conducted in Google Scholar, PubMed, and EMBASE databases. Additional broad hand searches were conducted with the additional terms etiology, diagnose, treatment. Results: Most evidence on the pathophysiology of somatosensory tinnitus suggests that somatic modulations are the result of altered or cross-modal synaptic activity within the dorsal cochlear nucleus or between the auditory nervous system and other sensory subsystems of central nervous system (e.g., visual or tactile). Presentations of somatosensory tinnitus are varied and evidence for the various approaches to treatment promising but limited. Discussion and Conclusions: Despite the apparent prevalence of somatosensory tinnitus its underlying neural processes are still not well understood. Necessary involvement of multidisciplinary teams in its diagnosis and treatment has led to a large heterogeneity of approaches whereby tinnitus improvement is often only a secondary effect. Hence there are no evidence-based clinical guidelines, and patient care is empirical rather than research-evidence-based. Somatic testing should receive further attention considering the breath of evidence on the ability of patients to modulate their tinnitus through manouvers. Specific questions for further research and review are indicated.

Does Spanish instruction for emergency medicine resident physicians improve patient satisfaction in the emergency department and adherence to medical recommendations?

BACKGROUND: After emergency department (ED) discharge, Spanish-speaking patients with limited English proficiency are less likely than English-proficient patients to be adherent to medical recommendations and are more likely to be dissatisfied with their visit. OBJECTIVES: To determine if integrating a longitudinal medical Spanish and cultural competency curriculum into emergency medicine residency didactics improves patient satisfaction and adherence to medical recommendations in Spanish-speaking patients with limited English proficiency. METHODS: Our ED has two Emergency Medicine Residency Programs, University Campus (UC) and South Campus (SC). SC program incorporates a medical Spanish and cultural competency curriculum into their didactics. Real-time Spanish surveys were collected at SC ED on patients who self-identified as primarily Spanish-speaking during registration and who were treated by resident physicians from both residency programs. Surveys assessed whether the treating resident physician communicated in the patient's native Spanish language. Follow-up phone calls assessed patient satisfaction and adherence to discharge instructions. RESULTS: Sixty-three patients self-identified as primarily Spanish-speaking from August 2014 to July 2015 and were initially included in this pilot study. Complete outcome data were available for 55 patients. Overall, resident physicians spoke Spanish 58% of the time. SC resident physicians spoke Spanish with 66% of the patients versus 45% for UC resident physicians. Patients rated resident physician Spanish ability as very good in 13% of encounters - 17% for SC versus 5% for UC. Patient satisfaction with their ED visit was rated as very good in 35% of encounters - 40% for SC resident physicians versus 25% for UC resident physicians. Of the 13 patients for whom Spanish was the language used during the medical encounter who followed medical recommendations, ten (77%) of these encounters were with SC resident physicians and three (23%) encounters were with UC resident physicians. CONCLUSION: Preliminary data suggest that incorporating Spanish language and cultural competency into residency training has an overall beneficial effect on patient satisfaction and adherence to medical recommendations in Spanish-speaking patients with limited English proficiency.

Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways.

Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local pro-inflammatory signature with significantly higher TNF-α levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity.

Mechanisms involved in quinolone resistance in Mycoplasma mycoides subsp. capri.

Mycoplasma mycoides subsp. capri is a causative agent of contagious agalactia in goats. In this study, M. mycoides subsp. capri mutants were selected for resistance to fluoroquinolones (norfloxacin, enrofloxacin and ciprofloxacin) by serial passes in broth with increasing concentrations of antibiotic. Mutations conferring cross-resistance to the three fluoroquinolones were found in the quinolone resistance determining regions of the four genes encoding DNA gyrase and topoisomerase IV. Different mutations in the DNA gyrase GyrA subunit suggest a different mechanism of inhibition between norfloxacin and the other tested fluoroquinolones. The presence of an adenosine triphosphate-dependent efflux system was suggested through the use of the inhibitor orthovanadate.

Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one.

In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one (compound 2) as an antibiotic effective in vivo against methicillin-resistant Staphylococcus aureus (MRSA). This antibiotic impairs cell-wall biosynthesis as documented by functional assays, showing binding of 2 to penicillin-binding protein (PBP) 2a. We document that the antibiotic also inhibits PBP1 of S. aureus, indicating a broad targeting of structurally similar PBPs by this antibiotic. This class of antibiotics holds promise in fighting MRSA infections.

Structure-activity relationship for the oxadiazole class of antibiotics.

The structure-activity relationship (SAR) for the newly discovered oxadiazole class of antibiotics is described with evaluation of 120 derivatives of the lead structure. This class of antibiotics was discovered by in silico docking and scoring against the crystal structure of a penicillin-binding protein. They impair cell-wall biosynthesis and exhibit activities against the Gram-positive bacterium Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant and linezolid-resistant S. aureus. 5-(1H-Indol-5-yl)-3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a high volume of distribution, and low clearance. This antibiotic is bactericidal and is orally bioavailable in mice. This class of antibiotics holds great promise in recourse against infections by MRSA.

Discovery of a new class of non-ß-lactam inhibitors of penicillin-binding proteins with Gram-positive antibacterial activity.

Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-ß-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin- and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.

Class D ß-lactamases: are they all carbapenemases?

Carbapenem-hydrolyzing class D ß-lactamases (CHDLs) are enzymes of the utmost clinical importance due to their ability to produce resistance to carbapenems, the antibiotics of last resort for the treatment of various life-threatening infections. The vast majority of these enzymes have been identified in Acinetobacter spp., notably in Acinetobacter baumannii. The OXA-2 and OXA-10 enzymes predominantly occur in Pseudomonas aeruginosa and are currently classified as narrow-spectrum class D ß-lactamases. Here we demonstrate that when OXA-2 and OXA-10 are expressed in Escherichia coli strain JM83, they produce a narrow-spectrum antibiotic resistance pattern. When the enzymes are expressed in A. baumannii ATCC 17978, however, they behave as extended-spectrum ß-lactamases and confer resistance to carbapenem antibiotics. Kinetic studies of OXA-2 and OXA-10 with four carbapenems have demonstrated that their catalytic efficiencies with these antibiotics are in the same range as those of some recognized class D carbapenemases. These results are in disagreement with the classification of the OXA-2 and OXA-10 enzymes as narrow-spectrum ß-lactamases, and they suggest that other class D enzymes that are currently regarded as noncarbapenemases may in fact be CHDLs.

Acquired Class D ß-Lactamases.

The Class D ß-lactamases have emerged as a prominent resistance mechanism against ß-lactam antibiotics that previously had efficacy against infections caused by pathogenic bacteria, especially by Acinetobacter baumannii and the Enterobacteriaceae. The phenotypic and structural characteristics of these enzymes correlate to activities that are classified either as a narrow spectrum, an extended spectrum, or a carbapenemase spectrum. We focus on Class D ß-lactamases that are carried on plasmids and, thus, present particular clinical concern. Following a historical perspective, the susceptibility and kinetics patterns of the important plasmid-encoded Class D ß-lactamases and the mechanisms for mobilization of the chromosomal Class D ß-lactamases are discussed.

Novel aminoglycoside 2''-phosphotransferase identified in a gram-negative pathogen.

Aminoglycoside 2″-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci. We describe a novel aminoglycoside 2″-phosphotransferase from the Gram-negative pathogen Campylobacter jejuni, which shares 78% amino acid sequence identity with the APH(2″)-Ia domain of the bifunctional aminoglycoside-modifying enzyme aminoglycoside (6') acetyltransferase-Ie/aminoglycoside 2″-phosphotransferase-Ia or AAC(6')-Ie/APH(2″)-Ia from Gram-positive cocci, which we called APH(2″)-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin, but not to any of the 4,5-disubstituted antibiotics tested. Steady-state kinetic studies demonstrated that GTP, and not ATP, is the preferred cosubstrate for APH(2″)-If. The enzyme phosphorylates the majority of 4,6-disubstituted aminoglycosides with high catalytic efficiencies (k(cat)/K(m) = 10(5) to 10(7) M(-1) s(-1)), while the catalytic efficiencies against the 4,6-disubstituted antibiotics amikacin and isepamicin are 1 to 2 orders of magnitude lower, due mainly to the low apparent affinities of these substrates for the enzyme. Both 4,5-disubstituted antibiotics and the atypical aminoglycoside neamine are not substrates of APH(2″)-If, but are inhibitors. The antibiotic susceptibility and substrate profiles of APH(2″)-If are very similar to those of the APH(2″)-Ia phosphotransferase domain of the bifunctional AAC(6')-Ie/APH(2″)-Ia enzyme.

Antibiotic resistance and substrate profiles of the class A carbapenemase KPC-6.

The class A carbapenemase KPC-6 produces resistance to a broad range of ß-lactam antibiotics. This enzyme hydrolyzes penicillins, the monobactam aztreonam, and carbapenems with similar catalytic efficiencies, ranging from 10(5) to 10(6) M(-1) s(-1). The catalytic efficiencies of KPC-6 against cephems vary to a greater extent, ranging from 10(3) M(-1) s(-1) for the cephamycin cefoxitin and the extended-spectrum cephalosporin ceftazidime to 10(5) to 10(6) M(-1) s(-1) for the narrow-spectrum and some of the extended-spectrum cephalosporins.

Class A carbapenemase FPH-1 from Francisella philomiragia.

FPH-1 is a new class A carbapenemase from Francisella philomiragia. It produces high-level resistance to penicillins and the narrow-spectrum cephalosporin cephalothin and hydrolyzes these ß-lactam antibiotics with catalytic efficiencies of 10(6) to 10(7) M(-1) s(-1). When expressed in Escherichia coli, the enzyme confers resistance to clavulanic acid, tazobactam, and sulbactam and has K(i) values of 7.5, 4, and 220 µM, respectively, against these inhibitors. FPH-1 increases the MIC of the monobactam aztreonam 256-fold and the MIC of the broad-spectrum cephalosporin ceftazidime 128-fold, while the MIC of cefoxitin remains unchanged. MICs of the carbapenem antibiotics imipenem, meropenem, doripenem, and ertapenem are elevated 8-, 8-, 16-, and 64-fold, respectively, against an E. coli JM83 strain producing the FPH-1 carbapenemase. The catalytic efficiencies of the enzyme against carbapenems are in the range of 10(4) to 10(5) M(-1) s(-1). FPH-1 is 77% identical to the FTU-1 ß-lactamase from Francisella tularensis and has low amino acid sequence identity with other class A ß-lactamases. Together with FTU-1, FPH-1 constitutes a new branch of the prolific and ever-expanding class A ß-lactamase tree.